Oncofocus Patient Test Report

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Oncofocus Patient Test Report Oncologica UK Ltd Suite 15-16, The Science Village Chesterford Research Park Cambridge, CB10 1XL, UK Tel: +44(0)1223 785327 Email: [email protected]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 1 of 67

SUBJECT INFORMATION SITE INFORMATION : _ Site ID: _ ( ) Date of B irth: ______(dd/mm/yyyy) Phone: ______: ______Gender: M F

SPECIMEN INFORMATION

No.: ______Date Specimen Received: _____ Date Reported: ______

Variant Summary

Sample Cancer Type: Melanoma

 In this cancer  In other cancer  In this cancer type and  Contraindicated  Both for use and  No evidence type type other cancer types contraindicated

Global Gene Variant EMA US-FDA ESMO US-NCCN Clinical Trials

BRAF V600E mutation     

ALK fusion     

ERBB2 amplification     

EGFR exon 19 deletion     

ONC15-: 0000 www.oncologica.com Other mutations, copy number variations, or fusions that were detected but not classified by the Oncofocus Reporter as a genetic driver of cancer are not listed in the results section of this report. All other genes listed in the Test Description that do not appear in the results section either did not have a detected variant or the variant is not classified as a genetic driver for cancer.

DISCLAIMER: The data presented here is a result of the curation of published data sources as of 2015.09(005), but may not be exhaustive. Oncologica UK Ltd Suite 15-16, The Science Village Chesterford Research Park Cambridge, CB10 1XL, UK Tel: +44(0)1223 785327 Email: [email protected]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 2 of 67 Relevant Therapy Summary

 In this cancer  In other cancer  In this cancer type and  Contraindicated  Both for use and  No evidence type type other cancer types contraindicated

BRAF V600E mutation

Global Relevant Therapy EMA US-FDA ESMO US-NCCN Clinical Trials*

vemurafenib      (IV)

dabrafenib      (II)

trametinib     

dabrafenib + trametinib      (II)

ipilimumab     

nivolumab     

pembrolizumab     

binimetinib + encorafenib, encorafenib, vemurafenib      (III)

dabrafenib + trametinib, trametinib      (III)

aldesleukin + ipilimumab + chemotherapy +      (II) infiltrating lymphocytes

aldesleukin + vemurafenib + chemotherapy +      (II) infiltrating lymphocytes

BGJ-398 + binimetinib + encorafenib, binimetinib + buparlisib + encorafenib, binimetinib + capmatinib +      (II) encorafenib, binimetinib + encorafenib, binimetinib + encorafenib + ribociclib

dabrafenib, dabrafenib + trametinib      (II)

dabrafenib, dabrafenib + trametinib, trametinib      (II)

dabrafenib, vemurafenib      (II)

erlotinib, pertuzumab + trastuzumab, vemurafenib,      (II) vismodegib

vemurafenib + acitretin      (II)

AB-024      (I/II)

* Most advanced phase (IV, III, II/III, II, I/II, I) is shown and multiple clinical trials may be available. See global clinical trials section in the pages to follow.

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 3 of 67 Relevant Therapy Summary (continued)

 In this cancer  In other cancer  In this cancer type and  Contraindicated  Both for use and  No evidence type type other cancer types contraindicated

BRAF V600E mutation (continued)

Global Relevant Therapy EMA US-FDA ESMO US-NCCN Clinical Trials*

binimetinib + encorafenib, binimetinib + encorafenib      (I/II) + ribociclib

buparlisib + vemurafenib      (I/II)

cetuximab + vemurafenib + irinotecan      (I/II)

dabrafenib + durvalumab + trametinib, durvalumab +      (I/II) trametinib

dabrafenib + ipilimumab      (I/II)

dabrafenib + navitoclax + trametinib      (I/II)

dabrafenib + pembrolizumab + trametinib      (I/II)

dabrafenib + trametinib + hydroxychloroquine      (I/II)

dabrafenib + trametinib + uprosertib      (I/II)

durvalumab + epacadostat      (I/II)

epacadostat + nivolumab      (I/II)

interferon alpha-2b + vemurafenib      (I/II)

LNP3794      (I/II)

nivolumab + urelumab      (I/II)

palbociclib      (I/II)

peginterferon alfa-2b + vemurafenib      (I/II)

vemurafenib + chemotherapy + infiltrating      (I/II) lymphocytes

vemurafenib + decitabine      (I/II)

alpelisib + binimetinib      (I)

* Most advanced phase (IV, III, II/III, II, I/II, I) is shown and multiple clinical trials may be available. See global clinical trials section in the pages to follow.

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 4 of 67 Relevant Therapy Summary (continued)

 In this cancer  In other cancer  In this cancer type and  Contraindicated  Both for use and  No evidence type type other cancer types contraindicated

BRAF V600E mutation (continued)

Global Relevant Therapy EMA US-FDA ESMO US-NCCN Clinical Trials*

AT-13387 + dabrafenib + trametinib      (I)

atezolizumab + cobimetinib      (I)

atezolizumab + cobimetinib + vemurafenib,      (I) atezolizumab + vemurafenib

BGB-283      (I)

BVD-523      (I)

CART-GD2 + vemurafenib      (I)

cetuximab + KTN-3379, erlotinib + KTN-3379, KTN-3379, KTN-3379 + trastuzumab, KTN-3379 +      (I) vemurafenib

chemotherapy + SCH-900353, pembrolizumab +      (I) SCH-900353, ridaforolimus + SCH-900353

CM-24      (I)

crizotinib + dasatinib      (I)

crizotinib + vemurafenib, sorafenib + vemurafenib      (I)

dabrafenib + ipilimumab, dabrafenib + ipilimumab +      (I) trametinib

dabrafenib + ipilimumab, dabrafenib + ipilimumab +      (I) trametinib, ipilimumab, ipilimumab + trametinib

dabrafenib + midazolam + rosuvastatin calcium      (I)

dabrafenib + pazopanib      (I)

dabrafenib + rabeprazole sodium + rifampicin      (I)

everolimus + vemurafenib, temsirolimus +      (I) vemurafenib

* Most advanced phase (IV, III, II/III, II, I/II, I) is shown and multiple clinical trials may be available. See global clinical trials section in the pages to follow.

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 5 of 67 Relevant Therapy Summary (continued)

 In this cancer  In other cancer  In this cancer type and  Contraindicated  Both for use and  No evidence type type other cancer types contraindicated

BRAF V600E mutation (continued)

Global Relevant Therapy EMA US-FDA ESMO US-NCCN Clinical Trials*

HM-95573      (I)

MLN-2480      (I)

RO-5126766      (I)

trametinib + radiation therapy      (I)

vemurafenib + chemotherapy      (I)

vemurafenib + hydroxychloroquine      (I)

vemurafenib + rifampicin      (I)

vemurafenib + XL-888      (I)

ALK fusion

Global Relevant Therapy EMA US-FDA ESMO US-NCCN Clinical Trials*

crizotinib      (II)

ceritinib      (II)

entrectinib      (I/II)

TSR-011      (I/II)

ceritinib + chemotherapy      (I)

crizotinib + dasatinib      (I)

crizotinib + pazopanib, crizotinib + pazopanib +      (I) pemetrexed, crizotinib + pemetrexed

* Most advanced phase (IV, III, II/III, II, I/II, I) is shown and multiple clinical trials may be available. See global clinical trials section in the pages to follow.

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 6 of 67 Relevant Therapy Summary (continued)

 In this cancer  In other cancer  In this cancer type and  Contraindicated  Both for use and  No evidence type type other cancer types contraindicated

ERBB2 amplification

Global Relevant Therapy EMA US-FDA ESMO US-NCCN Clinical Trials*

ado-trastuzumab emtansine     

trastuzumab     

trastuzumab + docetaxel     

trastuzumab + paclitaxel     

lapatinib     

trastuzumab + aromatase inhibitor     

trastuzumab + carboplatin + docetaxel     

pertuzumab + trastuzumab + docetaxel     

lapatinib + trastuzumab     

pertuzumab + trastuzumab + chemotherapy     

trastuzumab + chemotherapy     

pertuzumab     

lapatinib + capecitabine     

pertuzumab + trastuzumab     

pertuzumab + trastuzumab + paclitaxel     

trastuzumab + capecitabine     

trastuzumab + chemotherapy (other)     

trastuzumab + cisplatin + fluoropyrimidine     

trastuzumab + vinorelbine     

erlotinib, pertuzumab + trastuzumab, vemurafenib,      (II) vismodegib

* Most advanced phase (IV, III, II/III, II, I/II, I) is shown and multiple clinical trials may be available. See global clinical trials section in the pages to follow.

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 7 of 67 Relevant Therapy Summary (continued)

 In this cancer  In other cancer  In this cancer type and  Contraindicated  Both for use and  No evidence type type other cancer types contraindicated

ERBB2 amplification (continued)

Global Relevant Therapy EMA US-FDA ESMO US-NCCN Clinical Trials*

CART-ERBB2      (I/II)

MSC-2363318A      (I)

EGFR exon 19 deletion

Global Relevant Therapy EMA US-FDA ESMO US-NCCN Clinical Trials*

afatinib      (II)

erlotinib     

gefitinib     

afatinib + chemotherapy     

erlotinib + chemotherapy     

erlotinib, pertuzumab + trastuzumab, vemurafenib,      (II) vismodegib

CLR-457      (I/II)

EGF-816      (I/II)

epitinib      (I)

erlotinib + pralatrexate      (I)

MSC-2363318A      (I)

* Most advanced phase (IV, III, II/III, II, I/II, I) is shown and multiple clinical trials may be available. See global clinical trials section in the pages to follow.

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 8 of 67 Current EMA Information

 In this cancer type  In other cancer type  In this cancer type and other cancer types  Contraindicated

EMA information is current as of 2015-05-01. For the most up-to-date information, search www.ema.europa.eu/ema.

BRAF V600E mutation

 dabrafenib

Cancer type: Melanoma Label as of: 2015-06-17 Variant class: BRAF V600 mutation Reference: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002604/WC500149671.pdf

 trametinib

Cancer type: Melanoma Label as of: 2015-02-04 Variant class: BRAF V600 mutation Reference: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002643/WC500169657.pdf

 vemurafenib

Cancer type: Melanoma Label as of: 2015-06-03 Variant class: BRAF V600 mutation Reference: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002409/WC500124317.pdf

ALK fusion

 crizotinib

Cancer type: Non-Small Cell Lung Cancer Label as of: 2015-06-08 Variant class: ALK positive Reference: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002489/WC500134759.pdf

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 9 of 67

ERBB2 amplification

 ado-trastuzumab emtansine

Cancer type: Breast Cancer Label as of: 2014-12-03 Variant class: ERBB2 amplification Reference: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002389/WC500158593.pdf

 lapatinib

Cancer type: Breast Cancer Label as of: 2015-03-30 Variant class: ERBB2 amplification Reference: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000795/WC500044957.pdf

 trastuzumab, trastuzumab + aromatase inhibitor, trastuzumab + carboplatin + docetaxel, trastuzumab + docetaxel, trastuzumab + paclitaxel

Cancer type: Breast Cancer, Gastric Cancer Label as of: 2015-04-21 Variant class: ERBB2 amplification Reference: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000278/WC500074922.pdf

EGFR exon 19 deletion

 afatinib

Cancer type: Non-Small Cell Lung Cancer Label as of: 2014-11-06 Variant class: EGFR activating mutation Reference: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002280/WC500152392.pdf

 erlotinib

Cancer type: Non-Small Cell Lung Cancer Label as of: 2014-02-03 Variant class: EGFR activating mutation Reference: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000618/WC500033994.pdf

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 10 of 67

EGFR exon 19 deletion (continued)

 gefitinib

Cancer type: Non-Small Cell Lung Cancer Label as of: 2014-11-11 Variant class: EGFR activating mutation Reference: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001016/WC500036358.pdf

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 11 of 67 Current US-FDA Information

 In this cancer type  In other cancer type  In this cancer type and other cancer types  Contraindicated

US-FDA information is current as of 2015-05-01. For the most up-to-date information, search www.fda.gov.

BRAF V600E mutation

 dabrafenib + trametinib, trametinib

Cancer type: Melanoma Label as of: 2014-01-08 Variant class: BRAF V600E mutation Indications and usage: MEKINIST is a kinase inhibitor indicated as a single agent and in combination with dabrafenib for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. The use in combination is based on the demonstration of durable response rate. Improvement in disease-related symptoms or overall survival has not been demonstrated for MEKINIST in combination with dabrafenib. Limitation of use: MEKINIST as a single agent is not indicated for treatment of patients who have received prior BRAF-inhibitor therapy.

Reference: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204114s001lbl.pdf

 dabrafenib, dabrafenib + trametinib

Cancer type: Melanoma Label as of: 2014-01-10 Variant class: BRAF V600E mutation Indications and usage:  TAFINLAR® is a kinase inhibitor indicated as a single agent for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.  TAFINLAR® in combination with trametinib is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. The use in combination is based on the demonstration of durable response rate. Improvement in disease-related symptoms or overall survival has not been demonstrated for TAFINLAR® in combination with trametinib. Limitation of Use: TAFINLAR® is not indicated for treatment of patients with wild-type BRAF melanoma.

Reference: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202806s002lbl.pdf

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 12 of 67

BRAF V600E mutation (continued)

 vemurafenib

Cancer type: Melanoma Label as of: 2014-11-25 Variant class: BRAF V600E mutation Indications and usage: ZELBORAF® is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. Limitation of Use: ZELBORAF® is not indicated for treatment of patients with wild-type BRAF melanoma.

Reference: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202429s006lbl.pdf

ALK fusion

 crizotinib

Cancer type: Non-Small Cell Lung Cancer Label as of: 2015-03-20 Variant class: ALK fusion Indications and usage: XALKORI® is a kinase inhibitor indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic kinase (ALK)-positive as detected by an FDA-approved test.

Reference: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/202570s013lbl.pdf

 ceritinib

Cancer type: Non-Small Cell Lung Cancer Label as of: 2014-04-29 Variant class: ALK positive Indications and usage: ZYKADIA™ is a kinase inhibitor indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This indication is approved under accelerated approval based on tumor response rate and duration of response. An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Reference: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205755s000lbl.pdf

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 13 of 67

ERBB2 amplification

 ado-trastuzumab emtansine

Cancer type: Breast Cancer Label as of: 2014-07-11 Variant class: ERBB2 amplification Indications and usage: KADCYLA® is a HER2-targeted antibody and microtubule inhibitor conjugate indicated, as a single agent, for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:  Received prior therapy for metastatic disease, or  Developed disease recurrence during or within six months of completing adjuvant therapy.

Reference: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125427s033lbl.pdf

 pertuzumab + trastuzumab + docetaxel

Cancer type: Breast Cancer Label as of: 2014-03-17 Variant class: ERBB2 amplification Indications and usage: PERJETA® is a HER2/neu receptor antagonist indicated for:  Use in combination with trastuzumab and docetaxel for treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease  Use in combination with trastuzumab and docetaxel as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. This indication is based on demonstration of an improvement in pathological complete response rate. No data are available demonstrating improvement in event-free survival or overall survival. Limitations of Use:  The safety of PERJETA® as part of a doxorubicin-containing regimen has not been established.  The safety of PERJETA® administered for greater than 6 cycles for early breast cancer has not been established.

Reference: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125409s104lbl.pdf

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 14 of 67

ERBB2 amplification (continued)

 trastuzumab

Cancer type: Breast Cancer, Gastric Cancer Label as of: 2015-04-23 Variant class: ERBB2 amplification Indications and usage: Herceptin® is a HER2/neu receptor antagonist indicated for:  the treatment of HER2 overexpressing breast cancer  the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma

Reference: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/103792s5327lbl.pdf

EGFR exon 19 deletion

 afatinib

Cancer type: Non-Small Cell Lung Cancer Label as of: 2013-11-21 Variant class: EGFR exon 19 deletion Indications and usage: GILOTRIF™ is a kinase inhibitor indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test Limitation of Use: Safety and efficacy of GILOTRIF have not been established in patients whose tumors have other EGFR mutations

Reference: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/201292s002lbl.pdf

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 15 of 67

EGFR exon 19 deletion (continued)

 erlotinib

Cancer type: Non-Small Cell Lung Cancer Label as of: 2015-04-27 Variant class: EGFR exon 19 deletion Indications and usage: TARCEVA® is a kinase inhibitor indicated for:  First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.  Maintenance treatment of patients with locally advanced or metastatic NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.  Treatment of locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen.  First-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer, in combination with gemcitabine. Limitations of Use:  TARCEVA® is not recommended for use in combination with platinum-based chemotherapy.  Safety and efficacy of TARCEVA® have not been evaluated as first-line treatment in patients with metastatic NSCLC whose tumors have EGFR mutations other than exon 19 deletions or exon 21 (L858R) substitution.

Reference: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021743s021lbl.pdf

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 16 of 67 Current ESMO Information

 In this cancer type  In other cancer type  In this cancer type and other cancer types  Contraindicated

ESMO information is current as of 2015-05-04. For the most up-to-date information, search www.esmo.org.

BRAF V600E mutation

 vemurafenib

Cancer type: Melanoma Variant class: BRAF V600 mutation ESMO Recommendation category: II, B

Population segment (Line of therapy):  Metastatic melanoma (First-line therapy)

Reference: ESMO Clinical Practice Guidelines - Cutaneous Melanoma [Ann Oncol 2012; 23 (Suppl 7): vii86-vii91.]

ALK fusion

 crizotinib

Cancer type: Non-Small Cell Lung Variant class: ALK fusion Cancer ESMO Recommendation category: I, A

Population segment (Line of therapy):  Metastatic NSCLC (First or second-line therapy)

Reference: ESMO Clinical Practice Guidelines - Metastatic Non-Small-Cell Lung Cancer [Ann Oncol (2014) 25 (suppl 3): iii27- iii39.]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 17 of 67

ERBB2 amplification

 trastuzumab + chemotherapy

Cancer type: Breast Cancer Variant class: ERBB2 amplification ESMO Recommendation category: I, A

Population segment (Line of therapy):  Primary breast cancer (Not specified)

Reference: ESMO Clinical Practice Guidelines - Primary Breast Cancer [Ann Oncol 2013; 24 (Suppl 6): vi7-vi23.]

 ado-trastuzumab emtansine

Cancer type: Breast Cancer Variant class: ERBB2 positive ESMO Recommendation category: I, A

Population segment (Line of therapy):  Progression after trastuzumab based therapy (Second-line therapy)

Reference: ESMO Clinical Practice Guidelines - ESO-ESMO Advanced Breast Cancer [Ann Oncol (2014) doi: 10.1093/annonc/ mdu385 and The Breast 2014, doi: 10.1016/j.breast.2014.08.009]

 pertuzumab + trastuzumab + chemotherapy

Cancer type: Breast Cancer Variant class: ERBB2 positive ESMO Recommendation category: I, A

Population segment (Line of therapy):  Previously untreated metastatic breast cancer (First-line therapy)

Reference: ESMO Clinical Practice Guidelines - ESO-ESMO Advanced Breast Cancer [Ann Oncol (2014) doi: 10.1093/annonc/ mdu385 and The Breast 2014, doi: 10.1016/j.breast.2014.08.009]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 18 of 67

ERBB2 amplification (continued)

 trastuzumab + chemotherapy

Cancer type: Breast Cancer Variant class: ERBB2 positive ESMO Recommendation category: I, A

Population segment (Line of therapy):  Metastatic breast cancer previously treated in the adjuvant setting (First-line therapy)  Metastatic breast cancer untreated with trastuzumab (First-line therapy)

Reference: ESMO Clinical Practice Guidelines - ESO-ESMO Advanced Breast Cancer [Ann Oncol (2014) doi: 10.1093/annonc/ mdu385 and The Breast 2014, doi: 10.1016/j.breast.2014.08.009]

 lapatinib + trastuzumab

Cancer type: Breast Cancer Variant class: ERBB2 positive ESMO Recommendation category: I, B

Population segment (Line of therapy):  Progression on trastuzumab (Not specified)

Reference: ESMO Clinical Practice Guidelines - ESO-ESMO Advanced Breast Cancer [Ann Oncol (2014) doi: 10.1093/annonc/ mdu385 and The Breast 2014, doi: 10.1016/j.breast.2014.08.009]

 pertuzumab

Cancer type: Breast Cancer Variant class: ERBB2 positive ESMO Recommendation category: II, C

Population segment (Line of therapy):  Metastatic breast cancer previously untreated with pertuzumab (After first-line therapy)

Reference: ESMO Clinical Practice Guidelines - ESO-ESMO Advanced Breast Cancer [Ann Oncol (2014) doi: 10.1093/annonc/ mdu385 and The Breast 2014, doi: 10.1016/j.breast.2014.08.009]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 19 of 67

EGFR exon 19 deletion

 afatinib

Cancer type: Non-Small Cell Lung Variant class: EGFR exon 19 deletion Cancer ESMO Recommendation category: I, A

Population segment (Line of therapy):  Metastatic NSCLC (First-line therapy)

Reference: ESMO Clinical Practice Guidelines - Metastatic Non-Small-Cell Lung Cancer [Ann Oncol (2014) 25 (suppl 3): iii27- iii39.]

 erlotinib

Cancer type: Non-Small Cell Lung Variant class: EGFR exon 19 deletion Cancer ESMO Recommendation category: I, A

Population segment (Line of therapy):  Metastatic NSCLC (First-line therapy)

Reference: ESMO Clinical Practice Guidelines - Metastatic Non-Small-Cell Lung Cancer [Ann Oncol (2014) 25 (suppl 3): iii27- iii39.]

 gefitinib

Cancer type: Non-Small Cell Lung Variant class: EGFR exon 19 deletion Cancer ESMO Recommendation category: I, A

Population segment (Line of therapy):  Metastatic NSCLC (First-line therapy)

Reference: ESMO Clinical Practice Guidelines - Metastatic Non-Small-Cell Lung Cancer [Ann Oncol (2014) 25 (suppl 3): iii27- iii39.]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 20 of 67

EGFR exon 19 deletion (continued)

 gefitinib

Cancer type: Non-Small Cell Lung Variant class: EGFR mutation Cancer ESMO Recommendation category: II, A

Population segment (Line of therapy):  Postoperative, early stages I or II in adjuvant setting (Not specified)

Reference: ESMO Clinical Practice Guidelines - Early-Stage and Locally Advanced (non-metastatic) Non-Small-Cell Lung Cancer [Ann Oncol 2013; 24 (Suppl 6): vi89-vi98.]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 21 of 67 Current US-NCCN Information

 In this cancer type  In other cancer type  In this cancer type and other cancer types  Contraindicated

US-NCCN information is current as of 2015-05-04. For the most up-to-date information, search www.nccn.org.

BRAF V600E mutation

 dabrafenib

Cancer type: Melanoma Variant class: BRAF V600 mutation US-NCCN Recommendation category: 1

Population segment (Line of therapy):  Advanced or metastatic melanoma (Not specified)

Reference: NCCN Guidelines® - Melanoma [Version 3.2015]

 dabrafenib + trametinib

Cancer type: Melanoma Variant class: BRAF V600 mutation US-NCCN Recommendation category: 1

Population segment (Line of therapy):  Advanced or metastatic melanoma (Not specified)

Reference: NCCN Guidelines® - Melanoma [Version 3.2015]

 ipilimumab

Cancer type: Melanoma Variant class: BRAF V600 mutation US-NCCN Recommendation category: 1

Population segment (Line of therapy):  Metastatic or unresectable melanoma (First-line or second-line therapy)

Reference: NCCN Guidelines® - Melanoma [Version 3.2015]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 22 of 67

BRAF V600E mutation (continued)

 nivolumab

Cancer type: Melanoma Variant class: BRAF V600 mutation US-NCCN Recommendation category: 1

Population segment (Line of therapy):  Metastatic or unresectable melanoma (First-line therapy)

Reference: NCCN Guidelines® - Melanoma [Version 3.2015]

 trametinib

Cancer type: Melanoma Variant class: BRAF V600 mutation US-NCCN Recommendation category: 1

Population segment (Line of therapy):  Advanced, metastatic melanoma (First-line therapy)

Reference: NCCN Guidelines® - Melanoma [Version 3.2015]

 vemurafenib

Cancer type: Melanoma Variant class: BRAF V600 mutation US-NCCN Recommendation category: 1

Population segment (Line of therapy):  Advanced or metastatic melanoma (First-line therapy)

Reference: NCCN Guidelines® - Melanoma [Version 3.2015]

 dabrafenib

Cancer type: Melanoma Variant class: BRAF V600 mutation US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Metastatic or unresectable disease, if not used as first-line (Second-line therapy)

Reference: NCCN Guidelines® - Melanoma [Version 3.2015]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 23 of 67

BRAF V600E mutation (continued)

 dabrafenib + trametinib

Cancer type: Melanoma Variant class: BRAF V600 mutation US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Metastatic or unresectable disease, if not used as first-line (Second-line therapy)

Reference: NCCN Guidelines® - Melanoma [Version 3.2015]

 nivolumab

Cancer type: Melanoma Variant class: BRAF V600 mutation US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Metastatic or unresectable disease (Second-line therapy)

Reference: NCCN Guidelines® - Melanoma [Version 3.2015]

 pembrolizumab

Cancer type: Melanoma Variant class: BRAF V600 mutation US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Metastatic or unresectable melanoma (First-line or second-line therapy)

Reference: NCCN Guidelines® - Melanoma [Version 3.2015]

 trametinib

Cancer type: Melanoma Variant class: BRAF V600 mutation US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Metastatic or unresectable disease intolerant to BRAF inhibitors (Second-line therapy)

Reference: NCCN Guidelines® - Melanoma [Version 3.2015]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 24 of 67

BRAF V600E mutation (continued)

 vemurafenib

Cancer type: Melanoma Variant class: BRAF V600 mutation US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Metastatic or unresectable disease, if not used as first-line (Second-line therapy)

Reference: NCCN Guidelines® - Melanoma [Version 3.2015]

 dabrafenib

Cancer type: Non-Small Cell Lung Variant class: BRAF V600E mutation Cancer US-NCCN Recommendation category: 2A

Population segment (Line of therapy): Not specified (Not specified)

Reference: NCCN Guidelines® - Non-Small Cell Lung Cancer [Version 6.2015]

 vemurafenib

Cancer type: Non-Small Cell Lung Variant class: BRAF V600E mutation Cancer US-NCCN Recommendation category: 2A

Population segment (Line of therapy): Not specified (Not specified)

Reference: NCCN Guidelines® - Non-Small Cell Lung Cancer [Version 6.2015]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 25 of 67

ALK fusion

 crizotinib

Cancer type: Non-Small Cell Lung Variant class: ALK fusion Cancer US-NCCN Recommendation category: 1

Population segment (Line of therapy): Non-squamous NSCLC (First-line therapy, Second-line therapy)

Reference: NCCN Guidelines® - Non-Small Cell Lung Cancer [Version 6.2015]

 ceritinib

Cancer type: Non-Small Cell Lung Variant class: ALK fusion Cancer US-NCCN Recommendation category: 2A

Population segment (Line of therapy): Metastatic NSCLC, disease progression on or are intolerant to crizotinib (Second-line therapy)

Reference: NCCN Guidelines® - Non-Small Cell Lung Cancer [Version 6.2015]

ERBB2 amplification

 pertuzumab + trastuzumab + docetaxel

Cancer type: Breast Cancer Variant class: ERBB2 amplification US-NCCN Recommendation category: 1

Population segment (Line of therapy):  Metastatic breast cancer (First-line therapy)

Reference: NCCN Guidelines® - Breast Cancer [Version 2.2015]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 26 of 67

ERBB2 amplification (continued)

 trastuzumab + chemotherapy

Cancer type: Breast Cancer Variant class: ERBB2 amplification US-NCCN Recommendation category: 1

Population segment (Line of therapy):  Tumors >1cm (Not specified)  One or more > 2mm ipsilateral axillary lymph node metastases (Not specified)

Reference: NCCN Guidelines® - Breast Cancer [Version 2.2015]

 ado-trastuzumab emtansine

Cancer type: Breast Cancer Variant class: ERBB2 amplification US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Metastatic breast cancer previously treated with trastuzumab-based regimen (Not specified)

Reference: NCCN Guidelines® - Breast Cancer [Version 2.2015]

 lapatinib + capecitabine

Cancer type: Breast Cancer Variant class: ERBB2 amplification US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Metastatic breast cancer previously treated with trastuzumab-based regimen (Not specified)

Reference: NCCN Guidelines® - Breast Cancer [Version 2.2015]

 lapatinib + trastuzumab

Cancer type: Breast Cancer Variant class: ERBB2 amplification US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Metastatic breast cancer previously treated with trastuzumab-based regimen (Not specified)

Reference: NCCN Guidelines® - Breast Cancer [Version 2.2015]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 27 of 67

ERBB2 amplification (continued)

 pertuzumab + trastuzumab

Cancer type: Breast Cancer Variant class: ERBB2 amplification US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Disease progression after treatment with trastuzumab-based therapy without pertuzumab (Not specified)

Reference: NCCN Guidelines® - Breast Cancer [Version 2.2015]

 pertuzumab + trastuzumab + chemotherapy

Cancer type: Breast Cancer Variant class: ERBB2 amplification US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Did not receive pertuzumab as part of neoadjuvant therapy (Neoadjuvant/adjuvant therapy)  Disease progression after treatment with trastuzumab-based therapy without pertuzumab (Not specified)

Reference: NCCN Guidelines® - Breast Cancer [Version 2.2015]

 pertuzumab + trastuzumab + paclitaxel

Cancer type: Breast Cancer Variant class: ERBB2 amplification US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Metastatic breast cancer (First-line therapy)

Reference: NCCN Guidelines® - Breast Cancer [Version 2.2015]

 trastuzumab

Cancer type: Breast Cancer Variant class: ERBB2 amplification US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Metastatic breast cancer (First-line therapy)

Reference: NCCN Guidelines® - Breast Cancer [Version 2.2015]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 28 of 67

ERBB2 amplification (continued)

 trastuzumab + capecitabine

Cancer type: Breast Cancer Variant class: ERBB2 amplification US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Metastatic breast cancer (First-line therapy)  Metastatic breast cancer previously treated with trastuzumab-based regimen (Not specified)

Reference: NCCN Guidelines® - Breast Cancer [Version 2.2015]

 trastuzumab + chemotherapy

Cancer type: Breast Cancer Variant class: ERBB2 amplification US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Tumors 0.6-1.0cm, node-negative (Not specified)  Smaller tumors that have less than or equal to 2mm axillary node metastases (Not specified)  Metastatic breast cancer (First-line therapy)  Metastatic breast cancer previously treated with a trastuzumab-based regimen (Not specified)  Inflammatory breast cancer (Not specified)

Reference: NCCN Guidelines® - Breast Cancer [Version 2.2015]

 trastuzumab + docetaxel

Cancer type: Breast Cancer Variant class: ERBB2 amplification US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Metastatic breast cancer (First-line therapy)

Reference: NCCN Guidelines® - Breast Cancer [Version 2.2015]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 29 of 67

ERBB2 amplification (continued)

 trastuzumab + paclitaxel

Cancer type: Breast Cancer Variant class: ERBB2 amplification US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Low-risk stage I disease (Neoadjuvant/adjuvant therapy)  Metastatic breast cancer (First-line therapy)

Reference: NCCN Guidelines® - Breast Cancer [Version 2.2015]

 trastuzumab + vinorelbine

Cancer type: Breast Cancer Variant class: ERBB2 amplification US-NCCN Recommendation category: 2A

Population segment (Line of therapy):  Metastatic breast cancer (First-line therapy)

Reference: NCCN Guidelines® - Breast Cancer [Version 2.2015]

 trastuzumab + cisplatin + fluoropyrimidine

Cancer type: Esophageal Cancer Variant class: ERBB2 positive US-NCCN Recommendation category: 1

Population segment (Line of therapy):  Locally advanced or metastatic adenocarcinoma (First-line therapy)

Reference: NCCN Guidelines® - Esophageal and Esophagogastric Junction Cancers [Version 3.2015]

 trastuzumab + cisplatin + fluoropyrimidine

Cancer type: Gastric Cancer Variant class: ERBB2 positive US-NCCN Recommendation category: 1

Population segment (Line of therapy):  Locally advanced or metastatic gastric cancer (First-line therapy)

Reference: NCCN Guidelines® - Gastric Cancer [Version 3.2015]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 30 of 67

ERBB2 amplification (continued)

 trastuzumab + chemotherapy (other)

Cancer type: Esophageal Cancer Variant class: ERBB2 positive US-NCCN Recommendation category: 2B

Population segment (Line of therapy):  Locally advanced or metastatic adenocarcinoma (Not specified)

Reference: NCCN Guidelines® - Esophageal and Esophagogastric Junction Cancers [Version 3.2015]

 trastuzumab + chemotherapy (other)

Cancer type: Gastric Cancer Variant class: ERBB2 positive US-NCCN Recommendation category: 2B

Population segment (Line of therapy):  Locally advanced or metastatic gastric cancer (Not specified)

Reference: NCCN Guidelines® - Gastric Cancer [Version 3.2015]

EGFR exon 19 deletion

 afatinib

Cancer type: Non-Small Cell Lung Variant class: EGFR exon 19 deletion Cancer US-NCCN Recommendation category: 1

Population segment (Line of therapy): Metastatic non-squamous NSCLC (First-line therapy)

Reference: NCCN Guidelines® - Non-Small Cell Lung Cancer [Version 6.2015]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 31 of 67

EGFR exon 19 deletion (continued)

 erlotinib

Cancer type: Non-Small Cell Lung Variant class: EGFR exon 19 deletion Cancer US-NCCN Recommendation category: 1

Population segment (Line of therapy): Advanced, recurrent, or metastatic non-squamous NSCLC (First-line therapy)

Reference: NCCN Guidelines® - Non-Small Cell Lung Cancer [Version 6.2015]

 afatinib

Cancer type: Non-Small Cell Lung Variant class: EGFR exon 19 deletion Cancer US-NCCN Recommendation category: 2A

Population segment (Line of therapy): Not specified (Subsequent therapy)

Reference: NCCN Guidelines® - Non-Small Cell Lung Cancer [Version 6.2015]

 erlotinib

Cancer type: Non-Small Cell Lung Variant class: EGFR exon 19 deletion Cancer US-NCCN Recommendation category: 2A

Population segment (Line of therapy): Not specified (Subsequent therapy)

Reference: NCCN Guidelines® - Non-Small Cell Lung Cancer [Version 6.2015]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 32 of 67

EGFR exon 19 deletion (continued)

 afatinib + chemotherapy

Cancer type: Non-Small Cell Lung Variant class: EGFR exon 19 deletion Cancer US-NCCN Recommendation category: 2B

Population segment (Line of therapy): Advanced NSCLC (First-line therapy)

Reference: NCCN Guidelines® - Non-Small Cell Lung Cancer [Version 6.2015]

 erlotinib + chemotherapy

Cancer type: Non-Small Cell Lung Variant class: EGFR exon 19 deletion Cancer US-NCCN Recommendation category: 2B

Population segment (Line of therapy): Advanced NSCLC (First-line therapy)

Reference: NCCN Guidelines® - Non-Small Cell Lung Cancer [Version 6.2015]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 33 of 67 Current Global Clinical Trials Information

Global Clinical Trials information is current as of 2015-05-01. For the most up-to-date information regarding a particular trial, search www.clinicaltrials.gov by NCT ID or search local clinical trials authority website by local identifier listed in 'Other identifiers'.

BRAF V600E mutation

NCT01739764 Other identifiers: CANC - 3828, EudraCT Number: 2012-003144-80, Extension A Phase IV, PostMarketing, Open- (Rollover) Study, GO28399, NL43324.031.13, TrialTroveID-177920, UKCRN ID: 18402, Label, Extension (Rollover) Study of USMAVVEM Vemurafenib in Patients With BRAF V600 Mutation-Positive Malignancies Population segments: Line of therapy N/A, Stage IV Previously Enrolled in an Antecedent Phase: Vemurafenib Protocol IV Cancer type: Melanoma Therapy: vemurafenib

Variant class: BRAF V600 mutation Countries: Belarus, Brazil, Croatia, Cyprus, Egypt, Germany, Greece, Hungary, Israel, Italy, Netherlands, New Zealand, Republic of Korea, Russian Federation, Serbia, South Africa, Spain, United Kingdom, United States

US States: AR, CA, IA, NY, TX

US Contact: Hoffmann-La Roche Contact [888-662-6728; [email protected]]

NCT01898585 Other identifiers: ML28711, TrialTroveID-190333 An Open-Label, Single-Arm, Multicenter Study To Assess The Safety Of Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, Vemurafenib In Patients With Braf V600 Stage IV Mutation Positive Metastatic Melanoma Phase: In South Africa IV Cancer type: Melanoma Therapy: vemurafenib

Variant class: BRAF V600 mutation Country: South Africa

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 34 of 67

BRAF V600E mutation (continued)

NCT01990248 Other identifiers: GP28492, HELIOS ID HRC [004 621], NCRN 530, NCRN 530/ZeSS, ZeSS: A Prospective Observational ROCHE ZESS, TrialTroveID-195632, UKCRN ID13625, ZeSS Safety Study of Patients with BRAF- V600 Mutation-positive Unresectable Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, or Metastatic Melanoma Treated with Stage IV Vemurafenib (Zelboraf) Phase: IV Cancer type: Melanoma Therapy: vemurafenib Variant class: BRAF V600 mutation Countries: Austria, Belgium, Czech Republic, Germany, Italy, Netherlands, Poland, Sweden, United Kingdom

NCT01909453 Other identifiers: CMEK162B2301, COLUMBUS, EudraCT number: 2013-001176-38, A 2-part Phase III Randomized, Open NCRN567, NL45052.056.13, REec-2013-0533, TrialTroveID-185791, UCI-13-36, Label, Multicenter Study of LGX818 UKCRN ID: 14706 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in Patients Population segments: First line, Stage III, Stage IV With Unresectable or Metastatic BRAF Phase: V600 Mutant Melanoma Combination III of LGX818 used with MEK162 in BRAF Therapies: mutant unresectable skin cancer binimetinib + encorafenib, encorafenib, vemurafenib (COLUMBUS) Countries: Argentina, Australia, Canada, Colombia, Czech Republic, France, Germany, Cancer type: Melanoma Greece, Hungary, Israel, Italy, Japan, Mexico, Netherlands, Norway, Poland, Portugal, Republic of Korea, Russian Federation, Singapore, Slovakia, South Africa, Spain, Variant class: BRAF V600E mutation Sweden, Switzerland, Turkey, United Kingdom, United States

US States: AL, AR, AZ, CA, CO, FL, IA, IL, IN, LA, MA, MI, MN, MS, ND, NE, NJ, NY, OK, PA, TN, TX, VA, VT, WA

US Contact: Novartis Pharmaceuticals [888-669-6682]

NCT02416232 Other identifiers: 202105, TrialTroveID-255497 An Open Label Non Randomized Access Study of Trametinib for Patients With Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, Advanced Unresectable (Stage IIIc) Stage IV or Distant Metastatic (Stage IV) BRAF Phase: V600E/K Mutation Positive Cutaneous III Melanoma Therapies: dabrafenib + trametinib, trametinib Cancer type: Melanoma Country: France Variant class: BRAF V600E mutation

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 35 of 67

BRAF V600E mutation (continued)

NCT01667419 Other identifiers: 00040912, 101726, 12-166, 2012-0437, 201209116, BRIM8, Phase III, Randomized, Double- CTBE2013000226, EudraCT Number: 2011-004011-24, G027826, GO27826, Blind, Placebo-Controlled Study of NCRN442 BRIM 8, NL41606.058.12, TrialTroveID-152164, UKCRN ID 13620, Vemurafenib (RO5185426) Adjuvant VICCMEL1256 Therapy in Patients with Surgically- Resected, Cutaneous BRAF Mutant Population segments: Adjuvant, Stage II, Stage III Melanoma at High Risk for Recurrence Phase: III Cancer type: Melanoma Therapy: vemurafenib Variant class: BRAF V600E mutation Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Croatia, Czech Republic, Estonia, France, Germany, Ireland, Israel, Italy, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Russian Federation, Serbia, South Africa, Spain, Sweden, Switzerland, Ukraine, United Kingdom, United States

US States: AL, CA, CO, FL, IL, IN, MI, MO, NC, NJ, NY, PA, SC, TN

US Contact: Roche Reference Study ID Number: GO27826 [888-662-6728; [email protected]]

NCT01659151 Other identifiers: MCC#16992, MCC-16992, TrialTroveID-172519 A Phase II Clinical Trial of Vemurafenib With Lymphodepletion Plus Adoptive Cell Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, Transfer and High Dose IL-2 in Patients Stage IV With Metastatic Melanoma Phase: II Cancer type: Melanoma Therapy: aldesleukin + vemurafenib + chemotherapy + infiltrating lymphocytes Variant class: BRAF V600E mutation Country: United States

US State: FL

US Contact: Erica Royster [813-745-4279; [email protected]]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 36 of 67

BRAF V600E mutation (continued)

NCT01682213 Other identifiers: 12-124, TrialTroveID-174108 A Phase ll Trial of Adjuvant Dabrafenib (GSK2118436) in Patients with Surgically Population segments: Adjuvant, Stage III Resected AJCC Stage IIIC Melanoma Phase: Characterized by a BRAFV600E/K II mutation Therapy: dabrafenib Cancer type: Melanoma Country: United States Variant class: BRAF V600E mutation US State: NY

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

No NCT ID - see other identifier(s) Other identifiers: EudraCT Number: 2013-002616-28, N13NDT, TrialTroveID-213336 Cytoreductive treatment of dabrafenib combined with trametinib to allow Population segments: Neoadjuvant, Stage III, Stage IV complete surgical resection in patients with BRAF mutated, prior unresectable Phase: II stage III or IV melanoma Therapy: dabrafenib + trametinib Cancer type: Melanoma Country: Netherlands Variant class: BRAF V600E mutation

NCT01726738 Other identifiers: LCCC 1128, TrialTroveID-177461 LCCC 1128: Open Label Phase II Trial of the BRAF Inhibitor (Dabrafenib) Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, and the MEK Inhibitor (Trametinib) in Stage IV Unresectable Stage III and Stage IV Phase: BRAF Mutant Melanoma; Correlation II of Resistance With the Kinome and Therapy: Functional Mutations dabrafenib + trametinib Cancer type: Melanoma Country: United States

Variant class: BRAF V600E mutation US State: NC

US Contact: Dr. Carrie Lee [919-966-0405; [email protected]]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 37 of 67

BRAF V600E mutation (continued)

NCT01978236 Other identifiers: 116521, BRV116521, TrialTroveID-196800 An Open-Label, Multicentre, Corollary Study of Pre-Operative Therapy with Population segments: Adjuvant, CNS mets, Neoadjuvant, Stage IV Dabrafenib and the Combination of Phase: Dabrafenib with Trametinib in Subjects II with BRAF Mutation-Positive Metastatic Therapy: Melanoma to the Brain dabrafenib + trametinib Cancer type: Melanoma Country: United States

Variant class: BRAF V600E mutation US State: PA

US Contact: US GSK Clinical Trials Call Center [877-379-3718; [email protected]]

NCT02039947 Other identifiers: 117277, 2013-1020, BRF117277, COMBI-MB, EudraCT Number: BRF117277: A Phase II, Open-Label, 2013-003452-21, REec-2014-0719, TrialTroveID-199980 Multicentre Study of Dabrafenib Plus Trametinib in Subjects with BRAF Population segments: CNS mets, First line, Second line or greater/Refractory/ Mutation-Positive Melanoma that has Relapsed, Stage IV Metastasized to the Brain Phase: II Cancer type: Melanoma Therapy: dabrafenib + trametinib Variant class: BRAF V600E mutation Countries: Australia, Canada, France, Germany, Italy, Spain, United States

US States: AL, CO, GA, MA, NC, TX

US Contact: GSK Clinical Trials Call Center [877-379-3718; [email protected]]

NCT02083354 Other identifiers: 200104, TrialTroveID-204587 An Open-Label, Multi-Center Study to Investigate the Objective Response Population segments: First line, Stage III, Stage IV Rate of Dabrafenib in Combination With Phase: Trametinib in Subjects With BRAF V600 II E/K Mutation-Positive Acral Lentiginous Therapy: Melanoma dabrafenib + trametinib Cancer type: Melanoma Countries: Hong Kong, Republic of Korea, Taiwan, Thailand Variant class: BRAF V600E mutation

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 38 of 67

BRAF V600E mutation (continued)

NCT02196181 Other identifiers: AAAO7312, CMEL-14114, CTSU-S1320, NCI-2014-01470, S1320, A Randomized Phase II Trial of SWOG-S1320, TrialTroveID-199531 Intermittent Versus Continuous Dosing of Dabrafenib (NSC-763760) and Trametinib Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, (NSC-763093) in BRAF V600E/K Mutant Stage IV Melanoma Phase: II Cancer type: Melanoma Therapy: dabrafenib + trametinib Variant class: BRAF V600E mutation Country: United States

US States: AK, AL, AZ, CA, CO, DE, FL, GA, HI, IA, ID, IL, IN, KS, KY, MA, MD, ME, MI, MN, MO, MS, MT, NC, ND, NE, NJ, NV, NY, OH, OK, PA, SC, SD, TN, UT, VA, WA, WI, WY

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

NCT02231775 Other identifiers: 2014-0409, Combi-Neo, TrialTroveID-216204 Neoadjuvant and Adjuvant Dabrafenib and Trametinib Compared to Upfront Population segments: Adjuvant, Neoadjuvant, Stage III, Stage IV Surgery in Patients With Clinical Stage III Phase: or Oligometastatic Stage IV Melanoma II (Combi-Neo) Therapy: dabrafenib + trametinib Cancer type: Melanoma Country: United States Variant class: BRAF V600E mutation US State: TX

US Contact: Dr. Jennifer Wargo [713-745-1553]

NCT02296996 Other identifiers: Combi-Rechallenge, EudraCT number: 2013-004966-33, A Phase II Clinical Trial on the TrialTroveID-217245, UZB-2013-001, UZB-BN- 2013-001 Combination of Dabrafenib and Trametinib for BRAF-inhibitor Pretreated Population segments: Second line or greater/Refractory/Relapsed, Stage III, Stage IV Patients With Advanced BRAF V600 Exclusion criteria variant classes: Mutant Melanoma NRAS activating mutation, KRAS activating mutation, HRAS activating mutation Cancer type: Melanoma Phase: II Variant class: BRAF V600E mutation Therapy: dabrafenib + trametinib

Country: Belgium

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 39 of 67

BRAF V600E mutation (continued)

NCT02314143 Other identifiers: 116613, COMBAT 116613, EudraCT number 2012-004577-12, Phase II Biomarker Study Evaluating TrialTroveID-193492 The Upfront Combination Of BRAF Inhibitor Dabrafenib With MEK Inhibitor Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, Trametinib Versus The Combination Stage IV After Eight Weeks Of Monotherapy With Phase: Dabrafenib Or Trametinib In Patients With II Metastatic And Unresectable Stage III Or Therapies: IV Melanoma Harbouring An Activating dabrafenib, dabrafenib + trametinib, trametinib BRAF Mutation Country: France Cancer type: Melanoma Variant class: BRAF V600E mutation

NCT01701674 Other identifiers: CA184-213, MCC#17057, MCC-17057, TrialTroveID-175563 Co-stimulation With Ipilimumab to Enhance Lymphodepletion Plus Adoptive Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, Cell Transfer and High Dose IL-2 in Stage IV Patients With Metastatic Melanoma Phase: II Cancer type: Melanoma Therapy: aldesleukin + ipilimumab + chemotherapy + infiltrating lymphocytes Variant class: BRAF V600 mutation Country: United States

US State: FL

US Contact: Erica Royster [813-745-4279; [email protected]]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 40 of 67

BRAF V600E mutation (continued)

NCT02159066 Other identifiers: CLGX818X2109, EudraCT number: 2013-004552-38, LOGIC-2, A Phase II, Multi-center, Open-label NL48488.031.14, REec-2014-1129, REec-2014-1129, TrialTroveID-210645 Study of Sequential LGX818/MEK162 Combination Followed by a Rational Population segments: Second line or greater/Refractory/Relapsed, Stage III, Stage IV Combination With Targeted Agents After Phase: Progression, to Overcome Resistance in II Adult Patients With Locally Advanced or Therapies: Metastatic BRAF V600 Melanoma BGJ-398 + binimetinib + encorafenib, binimetinib + buparlisib + encorafenib, binimetinib + capmatinib + encorafenib, binimetinib + encorafenib, Cancer type: Melanoma binimetinib + encorafenib + ribociclib

Variant class: BRAF V600 mutation Countries: Australia, Canada, Germany, Italy, Netherlands, Spain, Switzerland, United States

US States: OR, TN

US Contact: Novartis Pharmaceuticals [888-669-6682]

NCT01972347 Other identifiers: 200332, ACTRN12613000737730, TrialTroveID-190566, An open label, single centre, phase II U1111-1143-0183 pilot study of neoadjuvant dabrafenib + trametinib in patients with resectable Population segments: Adjuvant, Neoadjuvant, Stage III AJCC Stage IIIB-C BRAF V600 mutation Phase: positive melanoma II Cancer type: Melanoma Therapy: dabrafenib + trametinib

Variant class: BRAF V600 mutation Country: Australia

NCT01701037 Other identifiers: NCI-2012-01699, TrialTroveID-175524, VICC MEL 1263, Biomarkers of Response and Resistance VICCMEL1263 to Sequential B-RAF and MEK Targeted Therapy in a Pre-Surgical Model of Population segments: Neoadjuvant, Stage II, Stage III, Stage IV Advanced, Operable Melanoma Phase: II Cancer type: Melanoma Therapies: dabrafenib, dabrafenib + trametinib Variant class: BRAF V600 mutation Country: United States

US State: TN

US Contact: VICC Clinical Trials Information Program [800-811-8480]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 41 of 67

BRAF V600E mutation (continued)

NCT02052193 Other identifiers: TrialTroveID-201783, ZDO 2012_PHOTOTOX Evaluation of Photosensitivity in Dabrafenib or Vemurafenib Treated Population segments: Line of therapy N/A, Stage III, Stage IV Metastatic Melanoma Patients - A Phase Phase: IIa/IIb Study II Cancer type: Melanoma Therapies: dabrafenib, vemurafenib

Variant class: BRAF V600 mutation Country: Germany

NCT01813214 Other identifiers: MLN28305, TrialTroveID-183514 Analysis of the Kinetics and Effects of Vemurafenib on Intratumoral Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, and Host Immunity in Patients With Stage IV Advanced BRAFV600 Mutant Melanoma: Phase: Implications for Combination With II Immunotherapy Therapy: vemurafenib Cancer type: Melanoma Country: United States Variant class: BRAF V600 mutation US States: DC, MA, TX, VA

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

NCT01942993 Other identifiers: 13-0427, GCO 13-0427, TrialTroveID-193899 The Effect of BRAF Inhibition With Vemurafenib On The Innate and Adaptive Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, Immune Systems in Patients With Stage IV Unresectable Stage III or Stage IV Phase: Melanoma Expressing a V600 BRAF II Mutation Therapy: vemurafenib Cancer type: Melanoma Country: United States Variant class: BRAF V600 mutation US State: NY

US Contact: Philip Friedlander [212-824-8588; [email protected]]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 42 of 67

BRAF V600E mutation (continued)

NCT02050321 Other identifiers: 1312167559, TrialTroveID-201701 A Phase II Study of Vemurafenib Combined With Acitretin in Patients With Population segments: Line of therapy N/A, Stage III, Stage IV Advanced Melanoma Phase: II Cancer type: Melanoma Therapy: vemurafenib + acitretin Variant class: BRAF exon 15 mutation Country: United States

US State: AZ

US Contact: Karrie Green [520-694-2873; [email protected]]

NCT01877811 Other identifiers: C32496/1105, TrialTroveID-167849 An Open-Label, Phase I/Phase II, Single-Agent Study of CEP-32496 in Population segments: Second line or greater/Refractory/Relapsed, Stage III, Stage IV Patients With Advanced Solid Tumors in Phase: Phase I and in Patients With Advanced I/II Melanoma and Metastatic Colorectal Therapy: Cancer With BRAF Mutation in Phase II AB-024 Cancer type: Melanoma Country: United States

Variant class: BRAF V600E mutation US States: CA, FL, MI, MO, PA

US Contact: Teva US Medical Information [800-896-5855]

NCT01512251 Other identifiers: CBKM120ZUS21T, CC#11952, Protocol 11952, TrialTroveID-160530 A Phase I/II Trial of BKM120 Combined With Vemurafenib (PLX4032) in Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, BRAFV600E/K Mutant Advanced Stage IV Melanoma Phase: I/II Cancer type: Melanoma Therapy: buparlisib + vemurafenib Variant class: BRAF V600E mutation Country: United States

US State: CA

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 43 of 67

BRAF V600E mutation (continued)

NCT02027961 Other identifiers: 13-606, 14851, 201312034, CD-ON-MEDI4736-1161, A Phase I Open-label Study of Safety and TrialTroveID-200244 Tolerability of MEDI4736 in Subjects with Metastatic or Unresectable Melanoma Population segments: Line of therapy N/A, Stage III, Stage IV in Combination with Dabrafenib and Phase: Trametinib or with Trametinib Alone I/II Cancer type: Melanoma Therapies: dabrafenib + durvalumab + trametinib, durvalumab + trametinib

Variant class: BRAF V600E mutation Countries: Canada, France, Italy, United Kingdom, United States

US States: AZ, CA, FL, IL, MA, MO, NY, OR

US Contact: AstraZeneca Clinical Study Information Center [877-240-9479; [email protected]]

NCT02200562 Other identifiers: HCI68132, TrialTroveID-213644 A Phase I/II Study of Concurrent Ipilimumab and Dabrafenib in Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, Unresectable Stage III or Stage IV Stage IV Melanoma Phase: I/II Cancer type: Melanoma Therapy: dabrafenib + ipilimumab Variant class: BRAF V600E mutation Country: United States

US State: UT

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

NCT01970956 Other identifiers: 13-424, 9466, NCI-2013-02103, TrialTroveID-196241 Phase I/II Study of Dabrafenib, Trametinib, and Navitoclax in BRAF Population segments: Second line or greater/Refractory/Relapsed, Stage III, Stage IV Mutant Melanoma and Other Solid Phase: Tumors I/II Cancer type: Melanoma Therapy: dabrafenib + navitoclax + trametinib

Variant class: BRAF V600E mutation Country: United States

US States: MA, NJ, TX

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 44 of 67

BRAF V600E mutation (continued)

NCT02130466 Other identifiers: 14-355, 3475-022, KN022, MK-3475-022/KEYNOTE-022, A Phase I/II Study to Assess the Safety TrialTroveID-208263 and Efficacy of MK-3475 in Combination With Trametinib and Dabrafenib in Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, Subjects With Advanced Melanoma Stage IV

Cancer type: Melanoma Phase: I/II Variant class: BRAF V600E mutation Therapy: dabrafenib + pembrolizumab + trametinib

Country: United States

US States: CA, MA

US Contact: Merck Sharp & Dohme Corp. [888-577-8839]

NCT02257424 Other identifiers: BAMM, TrialTroveID-218251, UPCC 02614 The BAMM trial: BRAF, autophagy and MEK inhibition in metastatic melanoma: Population segments: First line, Second line or greater/Refractory/Relapsed, Stage IV a phase I/II trial of dabrafenib, trametinib Phase: and hydroxychloroquine in patients with I/II advanced BRAF mutant melanoma Therapy: dabrafenib + trametinib + hydroxychloroquine Cancer type: Melanoma Country: United States Variant class: BRAF V600E mutation US State: PA

US Contact: Dr. Ravi Amaravadi [855-216-0098; [email protected]]

NCT02318277 Other identifiers: 2014-0753, INCB 24360-203, TrialTroveID-208833 A Phase I/II Study Exploring the Safety, Tolerability, and Efficacy of INCB024360 Population segments: EGFR, Second line or greater/Refractory/Relapsed, Squamous in Combination With MEDI4736 in Cell, Stage III, Stage IV Subjects With Selected Advanced Solid Phase: Tumors I/II Cancer type: Melanoma Therapy: durvalumab + epacadostat

Variant class: BRAF V600E mutation Country: United States

US States: CO, FL, NC, TX

US Contact: Incyte Corporation Call Center [855-463-3463]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 45 of 67

BRAF V600E mutation (continued)

NCT02327078 Other identifiers: AAAO2406, INCB 24360-204, TrialTroveID-209763 A Phase I/II Study of the Safety, Tolerability, and Efficacy of INCB24360 Population segments: Aggressive, ALK, Classical, Diffuse large B-cell lymphoma Administered in Combination With (DLBCL), EGFR, Nodular lymphocyte-predominant, Second line or greater/Refractory/ Nivolumab in Select Advanced Cancers Relapsed, Stage I, Stage II, Stage III, Stage IV, Triple receptor negative

Cancer type: Melanoma Phase: I/II Variant class: BRAF V600E mutation Therapy: epacadostat + nivolumab

Country: United States

US States: CA, NY, UT

US Contact: Incyte Call Center [855-463-3463]

NCT01943422 Other identifiers: 12-107, TrialTroveID-193931 Dose-seeking and Efficacy Study of the Combination of the BRAF Inhibitor Population segments: Maintenance/Consolidation, Stage III, Stage IV Vemurafenib and High-dose Interferon Phase: Alfa-2b for Therapy of Advanced I/II Melanoma Therapy: interferon alpha-2b + vemurafenib Cancer type: Melanoma Country: United States Variant class: BRAF V600E mutation US State: PA

US Contact: Dr. John Kirkwod [412-623-7707; [email protected]]

NCT02202200 Other identifiers: D20121106, OPTIMUM, TrialTroveID-213676 An Open Label Multicenter, Phase I-II Study With Tumor Molecular Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, Pharmacodynamic (MPD) Evaluation Stage IV and Pharmacokinetics of PD-0332991 in Exclusion criteria variant class: Patients Suffering Metastatic Melanoma CDKN2A wild type With BRAFv600 Mutated and CDKN2A Phase: Loss and Expression of Rb and Treated I/II by Vemurafenib Therapy: palbociclib Cancer type: Melanoma Country: France Variant class: BRAF V600E mutation

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 46 of 67

BRAF V600E mutation (continued)

NCT01876641 Other identifiers: 201304715, ML28604, TrialTroveID-188356 Phase I/II Study Epigenetic Modification of BRAF-mutated Metastatic Melanoma: Population segments: Second line or greater/Refractory/Relapsed, Stage IV Treatment of a Resistant Disease Using Phase: Decitabine Combined With Vemurafenib I/II Cancer type: Melanoma Therapy: vemurafenib + decitabine

Variant class: BRAF V600E mutation Country: United States

US State: IA

US Contact: Mohammed Milhem [319-356-2324; [email protected]]

NCT01543698 Other identifiers: 12-193, 2012-0238, CMEK162X2110, EudraCT A Phase Ib/II, Multicenter, Open-label, Number:2011-005875-17, J12117, MCC#17318, TrialTroveID-163520 Dose Escalation Study of LGX818 in Combination With MEK162 and LEE-011 Population segments: Recurrent, Second line or greater/Refractory/Relapsed, Stage in Adult Patients With BRAF V600- III, Stage IV Dependent Advanced Solid Tumors Phase: I/II Cancer type: Melanoma Therapies: binimetinib + encorafenib, binimetinib + encorafenib + ribociclib Variant class: BRAF V600 mutation Countries: Australia, Belgium, Canada, France, Italy, Spain, Switzerland

NCT01902173 Other identifiers: NCI-2013-01320, S1221, SWOG S1221, SWOG-S1221, Phase I/II Study of the Safety TrialTroveID-186975 and Efficacy of the AKT Inhibitor GSK2141795 in Combination With Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, Dabrafenib and Trametinib in Patients Stage IV With BRAF Mutant Cancer Phase: I/II Cancer type: Melanoma Therapy: dabrafenib + trametinib + uprosertib Variant class: BRAF V600 mutation Country: United States

US States: CA, CO, MI, OH, OR

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 47 of 67

BRAF V600E mutation (continued)

NCT01959633 Other identifiers: EudraCT Number: 2013-003730-33, TrialTroveID-195294, Phase I-II Study of the Combination VEMUPLINT Vemurafenib plus PEG-interferon in Advanced Melanoma Patients Harboring Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, the V600BRAF Mutation Stage IV

Cancer type: Melanoma Phase: I/II Variant class: BRAF V600 mutation Therapy: peginterferon alfa-2b + vemurafenib

Country: Italy

NCT02253992 Other identifiers: 17937, 2014-0651, CA186-107, EudraCT Number: 2014-002241-22, A Phase I/II Dose Escalation and Cohort TrialTroveID-217999 Expansion Study of the Safety and Tolerability of Urelumab Administered Population segments: Aggressive, ALK, Diffuse large B-cell lymphoma (DLBCL), in Combination with Nivolumab in EGFR, Extranodal marginal zone B-cell lymphoma (MALT), Follicular lymphoma Advanced/Metastatic Solid Tumors and (FL), Indolent, Mantle cell lymphoma (MCL), Second line or greater/Refractory/ B-cell Non-Hodgkins Lymphoma. Relapsed, Small lymphocytic lymphoma (SLL), Stage III, Stage IV, Waldenstrom`s macroglobulinemia (WM) Cancer type: Melanoma Phase: I/II Variant class: BRAF mutation Therapy: nivolumab + urelumab

Countries: Spain, United States

US States: FL, NY, TX

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

NCT02354690 Other identifiers: MM1414, TrialTroveID-220393 T-cell Therapy in Combination With Vemurafenib for Patients With BRAF Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, Mutated Metastatic Melanoma Stage IV

Cancer type: Melanoma Phase: I/II Variant class: BRAF mutation Therapy: vemurafenib + chemotherapy + infiltrating lymphocytes

Country: Denmark

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 48 of 67

BRAF V600E mutation (continued)

NCT02097225 Other identifiers: 14-186, 9557, NCI-2014-00615, TrialTroveID-205735 Phase I Study of AT13387 in Combination With Dabrafenib and Population segments: Second line or greater/Refractory/Relapsed, Stage III, Stage IV Trametinib in BRAF-Inhibitor Resistant Phase: Patients With BRAF-Mutant Melanoma I and Other Solid Tumors Therapy: AT-13387 + dabrafenib + trametinib Cancer type: Melanoma Country: United States Variant class: BRAF V600E mutation US States: FL, MA

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

No NCT ID - see other identifier(s) Other identifiers: ACTRN12613000198729, ANZMTG 01.10, CARPETS, Phase I study of safety and immune TrialTroveID-193667 effects of an escalating dose of autologous GD2 chimeric antigen Population segments: Line of therapy N/A, Stage III, Stage IV receptor-expressing peripheral blood T cells in patients with metastatic Phase: I melanoma Therapy: CART-GD2 + vemurafenib Cancer type: Melanoma Country: Australia Variant class: BRAF V600E mutation

NCT02014909 Other identifiers: KTN3379-CL-001, TrialTroveID-199352 Part I and Part II A Phase I Study to Evaluate the Safety, Tolerability, and Population segments: HER2 positive, Second line or greater/Refractory/Relapsed, Pharmacokinetics of KTN3379 in Adult Stage II, Stage III, Stage IV Subjects With Advanced Tumors Alone Phase: or With Chemotherapy I Cancer type: Melanoma Therapies: cetuximab + KTN-3379, erlotinib + KTN-3379, KTN-3379, KTN-3379 + trastuzumab, KTN-3379 + vemurafenib Variant class: BRAF V600E mutation Country: United States

US States: CO, CT, TN

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 49 of 67

BRAF V600E mutation (continued)

NCT02346955 Other identifiers: CB-24-001, TrialTroveID-249988 A Phase l First-In-Human, Multicenter, Open-Label, Multiple dose, Dose Population segments: Adenocarcinoma, Second line or greater/Refractory/Relapsed, Escalation, Efficacy, Tolerability, Safety Stage III, Stage IV and Pharmacokinetic Study of CM-24 in Phase: Cancer Patients with Selected Advanced I or Recurrent Malignancies Therapy: CM-24 Cancer type: Melanoma Country: Israel Variant class: BRAF V600E mutation

NCT01767454 Other identifiers: 115984, 13-339, 201306025, BRF115984, GSK 115984, MDACC Phase I Study of the BRAF Inhibitor 2012-0976, MSKCC 12-285, TrialTroveID-180298, VICCMEL1290 Dabrafenib + or - MEK Inhibitor Trametinib in Combination With Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, Ipilimumab for V600E/K Mutation Positive Stage IV Metastatic or Unresectable Melanoma Phase: I Cancer type: Melanoma Therapies: dabrafenib + ipilimumab, dabrafenib + ipilimumab + trametinib Variant class: BRAF V600E mutation Country: United States

US States: CA, MA, MO, NY, TN, TX

US Contact: US GSK Clinical Trials Call Center [877-379-3718; [email protected]]

NCT01938703 Other identifiers: 13-304, 9377, CTEP 9377, NCI-2013-01703, TrialTroveID-193550 A Sequential Safety and Biomarker Study of BRAF-MEK Inhibition on the Immune Population segments: Second line or greater/Refractory/Relapsed, Stage III, Stage IV Response in the Context of CTLA-4 Phase: Blockade for BRAF Mutant Melanoma. I Cancer type: Melanoma Therapies: dabrafenib + ipilimumab, dabrafenib + ipilimumab + trametinib, ipilimumab, ipilimumab + trametinib Variant class: BRAF V600E mutation Country: United States

US State: MA

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 50 of 67

BRAF V600E mutation (continued)

NCT01897116 Other identifiers: TrialTroveID-190137, UPCC 06613 A Phase I Trial of Vemurafenib and Hydroxychloroquine in Patients With Population segments: Second line or greater/Refractory/Relapsed, Stage IV Advanced BRAF Mutant Melanoma Phase: I Cancer type: Melanoma Therapy: vemurafenib + hydroxychloroquine Variant class: BRAF V600E mutation Country: United States

US State: PA

US Contact: Ravi Amaravadi [877-204-9213; [email protected]]

NCT01657591 Other identifiers: MCC-17013, TrialTroveID-172421 Phase l Study of Escalating Doses of XL888 With Vemurafenib for Patients with Population segments: First line, Second line or greater/Refractory/Relapsed, Stage III, Unresectable BRAF Mutated Stage III/IV Stage IV Melanoma Phase: I Cancer type: Melanoma Therapy: vemurafenib + XL-888 Variant class: BRAF V600E mutation Country: United States

US State: FL

US Contact: Leticia Tetteh [813-745-4617; [email protected]]

NCT01988896 Other identifiers: 13-223, 20132268, CT672, DFCI: 14-301, GP28363, GP28363-V2, A Phase Ib Study of the Safety HIC: 1403013518, Octopus, TrialTroveID-197176 and Pharmacology of MPDL3280A Administered with Cobimetinib in Population segments: ALK, EGFR, KRAS, Second line or greater/Refractory/Relapsed, Patients with Locally Advanced or Stage III, Stage IV Metastatic Solid Tumors Phase: I Cancer type: Melanoma Therapy: atezolizumab + cobimetinib Variant class: BRAF V600 mutation Countries: Australia, Canada, Germany, Republic of Korea, Singapore, United States

US States: CO, CT, MA, NC, NY, TN, TX, WA

US Contact: Reference Study ID Number: GP28363 [888-662-6728; [email protected]]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 51 of 67

BRAF V600E mutation (continued)

NCT01656642 Other identifiers: 2012-0588, GP28384, TrialTroveID-172390 A Phase Ib, Open-Label Study of The Safety and Pharmacology of MPDL3280A Population segments: First line, Stage IV Administered in Combination With Phase: Vemurafenib (Zelboraf) in Patients I With Previously Untreated BRAFV600- Therapies: Mutation Positive Metastatic Melanoma atezolizumab + cobimetinib + vemurafenib, atezolizumab + vemurafenib Cancer type: Melanoma Country: United States

Variant class: BRAF V600 mutation US States: FL, MA, TX

US Contact: Reference Study ID Number: GP28384 [888-662-6728; [email protected]]

NCT01907802 Other identifiers: 0C-13-5, 13-472, 13331, 9343, J13107, MAYO1Y13, A Phase I and Pharmacokinetic Study of MC1211, MC1211, NCI # 9343, NCI 9343, NCI#9343, NCI-2013-01338, PHI-73, Dabrafenib (GSK2118436B) in Patients TrialTroveID-191080 with BRAFV600X Mutations and Renal or Hepatic Dysfunction Population segments: First line, Metastatic, Papillary, Second line or greater/ Refractory/Relapsed, Stage III, Stage IV, Unresectable Cancer type: Melanoma Phase: I Variant class: BRAF V600 mutation Therapy: dabrafenib

Countries: Canada, United States

US States: CA, CO, FL, MA, MD, MI, MN, MO, OH, PA, WI

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

NCT01765543 Other identifiers: EudraCT Number: 2012-003142-33, GO28052, TrialTroveID-179892 A Phase I, Open-Label, Multicenter, Three-Period, One-Sequence Study To Population segments: Second line or greater/Refractory/Relapsed, Stage III, Stage IV Investigate The Effect Of Rifampin On Phase: The Pharmacokinetics Of A Single Oral I Dose Of 960 Mg Of Vemurafenib Therapy: vemurafenib + rifampicin Cancer type: Melanoma Countries: Brazil, Croatia, Egypt, South Africa, United States Variant class: BRAF V600 mutation US States: AR, OH, TX

US Contact: Reference Study ID Number: GO28052 [888-662-6728; [email protected]]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 52 of 67

BRAF V600E mutation (continued)

NCT01449058 Other identifiers: 11-490, 2013-0813, CMEK162X2109, CSET 1840, EudraCT Number: A Phase Ib Open-label, Multi-center, 2011-002578-21, HCI 53590, MSKCC-11-117, Novartis#CMEK162X2109, RECF2113, Dose Escalation and Expansion Study TrialTroveID-154495 of Orally Administered MEK162 Plus BYL719 in Adult Patients With Selected Population segments: High risk, Second line or greater/Refractory/Relapsed, Stage II, Advanced Solid Tumors Stage III, Stage IV, Triple receptor negative

Cancer type: Melanoma Phase: I Variant class: BRAF mutation Therapy: alpelisib + binimetinib

Countries: Australia, France, Spain, Switzerland, United Kingdom, United States

US States: CA, IL, MA, TX, UT

US Contact: Novartis Pharmaceuticals [862-778-8300]

NCT01781429 Other identifiers: 13-010, 13-254, 2013-0574, BVD-523-01, REFMAL 286 IST, Phase I Dose-Escalation, Safety, TrialTroveID-180584, VICCPHI1375 Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Population segments: Second line or greater/Refractory/Relapsed, Stage III, Stage IV Advanced Malignancies Phase: I Cancer type: Melanoma Therapy: BVD-523 Variant class: BRAF mutation Country: United States

US States: CA, CT, FL, MA, MO, NY, TN, TX

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

No NCT ID - see other identifier(s) Other identifiers: EudraCT Number: 2012-002695-13, MK8353-010, NL41947.031.12, A Phase I Study to Evaluate the Safety, TrialTroveID-222700 Tolerability and Efficacy of MK-8353 Combination Therapies in Subjects With Population segments: KRAS, Second line or greater/Refractory/Relapsed, Stage III, Advanced Solid Tumors Stage IV

Cancer type: Melanoma Phase: I Variant class: BRAF mutation Therapies: chemotherapy + SCH-900353, pembrolizumab + SCH-900353, ridaforolimus + SCH-900353

Country: Netherlands

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 53 of 67

BRAF V600E mutation (continued)

NCT02405065 Other identifiers: HM-RAFI-101, TrialTroveID-220532 Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics and Population segments: KRAS, Second line or greater/Refractory/Relapsed, Stage III, Anti-tumor Activity of HM95573 in Solid Stage IV Tumors Phase: I Cancer type: Melanoma Therapy: HM-95573 Variant class: BRAF mutation Country: Republic of Korea

NCT01425008 Other identifiers: C28001, EudraCT Number: 2012-003397-16, PMILLEN019, An Open-Label, Phase I, Dose Escalation TrialTroveID-152016 Study of MLN2480 in Patients With Relapsed or Refractory Solid Tumors Population segments: Locally advanced, Metastatic, Second line or greater/ Followed by a Dose Expansion Phase in Refractory/Relapsed, Stage III, Stage IV Patients With Metastatic Melanoma Phase: I Cancer type: Melanoma Therapy: MLN-2480 Variant class: BRAF mutation Countries: United Kingdom, United States

US States: CO, GA, IN, NY, PA, TX

US Contact: Millennium Medical and Drug Information Center [877-674-3784; [email protected]]

NCT02091141 Other identifiers: 1403013519, 2014-0459, ML28897, ML28897PRO/02, My Pathway: An Open Label Phase TrialTroveID-205033 IIa Study Evaluating Trastuzumab/ Pertuzumab, Erlotinib, Vemurafenib, Population segments: Second line or greater/Refractory/Relapsed, Stage IV and Vismodegib in Patients Who Have Phase: Advanced Solid Tumors With Mutations II or Gene Expression Abnormalities Therapies: Predictive of Response to One of These erlotinib, pertuzumab + trastuzumab, vemurafenib, vismodegib Agents Country: United States Cancer type: Unspecified Solid Tumor US States: AR, AZ, CA, CT, FL, GA, IL, MD, ND, OH, OK, PA, SD, TN, TX, VA, WA Variant class: BRAF activating mutation US Contact: Reference Study ID Number: ML28897 [888-662-6728; [email protected]]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 54 of 67

BRAF V600E mutation (continued)

NCT01787500 Other identifiers: 2012-0748, NCI-2013-00541, TrialTroveID-181751 A Phase I Trial of Vemurafenib in Combination With Cetuximab and Population segments: Line of therapy N/A, Stage III, Stage IV Irinotecan in Patients with BRAF V600 Exclusion criteria variant classes: Mutant Advanced Solid Malignancies KRAS G12 mutation, KRAS G13 mutation Cancer type: Unspecified Solid Tumor Phase: I/II

Variant class: BRAF V600 mutation Therapy: cetuximab + vemurafenib + irinotecan

Country: United States

US State: TX

US Contact: Dr. David S. Hong [713-593-1930]

No NCT ID - see other identifier(s) Other identifier: TrialTroveID-250171 A Phase I/II Study of LNP3794 in Patients with Advanced Solid Tumors having Population segments: Line of therapy N/A, Stage III, Stage IV RAS/BRAF Mutations Phase: I/II Cancer type: Unspecified Solid Tumor Therapy: LNP3794 Variant class: BRAF mutation Country: United Kingdom

NCT02015117 Other identifiers: 9458, NCI-2013-02343, OSU 13197, TrialTroveID-199440 A Phase I Study of Trametinib in Combination With Radiation Therapy for Population segments: CNS mets, Line of therapy N/A, Stage IV Brain Metastases From KRAS-, BRAF-, Phase: NRAS- or HRAS- Mutant Malignancies I Cancer type: Unspecified Cancer Therapy: trametinib + radiation therapy

Variant class: BRAF V600E mutation Country: United States

US State: OH

US Contact: Evan J. Wuthrick [614-293-3422; [email protected]]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 55 of 67

BRAF V600E mutation (continued)

NCT02082665 Other identifiers: 200919, TrialTroveID-204485 An Open-label Phase I Study to Evaluate the Effects of Dabrafenib (GSK2118436) Population segments: (N/A), Line of therapy N/A on the Single Dose Pharmacokinetics Phase: of an OATP1B1/1B3 Substrate and of I a CYP3A4 Substrate in Subjects With Therapy: BRAF V600 Mutation Positive Tumors dabrafenib + midazolam + rosuvastatin calcium Cancer type: Unspecified Cancer Country: Spain Variant class: BRAF V600 mutation

NCT01954043 Other identifiers: 200072, TrialTroveID-194828 An Open-label Study to Evaluate the Effects of a Potent CYP3A4 Inducer and Population segments: (N/A), Line of therapy N/A the Effects of a pH Elevating Agent on Phase: the Repeat Dose Pharmacokinetics of I Dabrafenib (GSK2118436) in Subjects Therapy: With BRAF V600 Mutation Positive dabrafenib + rabeprazole sodium + rifampicin Tumors Countries: Australia, United States Cancer type: Unspecified Solid Tumor US States: AZ, TX, WA Variant class: BRAF V600 mutation US Contact: US GSK Clinical Trials Call Center [877-379-3718; [email protected]]

NCT01767623 Other identifiers: 1803-7, EudraCT Number: 2012-003820-18, GO28053, An Open Label, Phase I Study to TrialTroveID-152167 Evaluate the Impact of Severe Hepatic Impairment on the Pharmacokinetics Population segments: Second line or greater/Refractory/Relapsed, Stage III, Stage IV and Safety of Vemurafenib in BRAF V600 Phase: mutation Positive Cancer Patients I Cancer type: Unspecified Solid Tumor Therapy: vemurafenib

Variant class: BRAF V600 mutation Countries: Australia, Israel, Russian Federation, Turkey, United Kingdom, United States

US State: CA

US Contact: Hoffmann-La Roche Contact [888-662-6728; [email protected]]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 56 of 67

BRAF V600E mutation (continued)

No NCT ID - see other identifier(s) Other identifiers: ACTRN12614001176651, BGB-283-AU-001, CT634, A Phase I Multicenter, Open-label, TrialTroveID-199386 Dose Escalation, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Population segments: Second line or greater/Refractory/Relapsed, Stage III, Stage IV Study of BGB-283 as a single agent in Patients with B-RAF or K-RAS mutations Phase: I

Cancer type: Unspecified Solid Tumor Therapy: BGB-283 Variant class: BRAF mutation Country: Australia

NCT01744652 Other identifiers: 2012-0721, NCI-2013-00071, TrialTroveID-178941 A Phase I Trial of Dasatinib in Combination With Crizotinib in Patients Population segments: Aggressive, Classical, Indolent, Nodular lymphocyte- With Advanced Malignancies predominant, Second line or greater/Refractory/Relapsed, Stage IV

Cancer type: Unspecified Solid Tumor Phase: I Variant class: BRAF mutation Therapy: crizotinib + dasatinib

Country: United States

US State: TX

US Contact: Dr. David S. Hong [800-392-1611]

NCT01531361 Other identifiers: 2011-1183, NCI-2012-00217, TrialTroveID-162168 A Phase I Trial of Sorafenib (CRAF, BRAF, KIT, RET, VEGFR, PDGFR Population segments: Adenocarcinoma, Papillary, Second line or greater/Refractory/ Inhibitor) or Crizotinib (MET, ALK, Relapsed, Stage III, Stage IV ROS1 Inhibitor) in Combination With Phase: Vemurafenib (BRAF Inhibitor) in Patients I With Advanced Malignancies Therapies: crizotinib + vemurafenib, sorafenib + vemurafenib Cancer type: Unspecified Cancer Country: United States Variant class: BRAF mutation US State: TX

US Contact: Dr. Filip Janku [713-563-1930]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 57 of 67

BRAF V600E mutation (continued)

NCT01713972 Other identifiers: MDACC 2012-0423, NCI-2012-01935, OSU 12066, OSU-12066, A Phase I Trial of GSK2118436 (BRAFi) TrialTroveID-174115 and Pazopanib in Patients With BRAF- mutated Advanced Malignant Tumors Population segments: Second line or greater/Refractory/Relapsed, Stage III, Stage IV

Cancer type: Unspecified Solid Tumor Phase: I Variant class: BRAF mutation Therapy: dabrafenib + pazopanib

Country: United States

US States: OH, TX

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

NCT01231594 Other identifiers: 114144, 12-016, 2010-0801, 44629, BRF114144, F14020, HCI A Rollover Study to provide Continued 44629, OSU-11024, REFMAL 223, TrialTroveID-137250, VICCMEL1209 Treatment with GSK2118436 to Subjects with BRAF Mutation-Positive Tumors Population segments: Line of therapy N/A, Stage IV

Cancer type: Unspecified Solid Tumor Phase: I Variant class: BRAF mutation Therapies: dabrafenib, dabrafenib + trametinib

Countries: Australia, Italy, Spain, United Kingdom, United States

US States: AZ, CA, FL, MI, NY, OH, OK, PA, SC, TN, TX, UT, WA

US Contact: US GSK Clinical Call Center [877-379-3718; [email protected]]

NCT01596140 Other identifiers: 2012-0153, TrialTroveID-167369 A Phase I Dose-Escalation Study of the BRAF Inhibitor Vemurafenib (Zelboraf) Population segments: Second line or greater/Refractory/Relapsed, Stage III, Stage IV in Combination With an mTOR Inhibitor, Phase: Everolimus (Afinitor) or Temsirolimus I (Torisel), in Subjects With Advanced Therapies: Cancer everolimus + vemurafenib, temsirolimus + vemurafenib Cancer type: Unspecified Solid Tumor Country: United States

Variant class: BRAF mutation US State: TX

US Contact: Dr. Vivek Subbiah [713-794-1226]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 58 of 67

BRAF V600E mutation (continued)

NCT02407509 Other identifiers: CCR3808, DDU RAF/MEK, EudraCT Number: 2012-001040-22, A Phase I Trial of RO5126766 (a TrialTroveID-206542 Dual RAF/MEK Inhibitor) Exploring Intermittent, Oral Dosing Regimens in Population segments: (N/A), Second line or greater/Refractory/Relapsed Patients With Solid Tumours or Multiple Phase: Myeloma I Cancer type: Unspecified Solid Tumor Therapy: RO-5126766

Variant class: BRAF mutation Country: United Kingdom

NCT01636622 Other identifiers: 2012-0394, NCI-2012-01221, TrialTroveID-171156 Phase I Study of the Combination of Vemurafenib With Carboplatin and Population segments: Aggressive, Classical, Indolent, Nodular lymphocyte- Paclitaxel in Patients With Advanced predominant, Second line or greater/Refractory/Relapsed, Stage III, Stage IV Malignancy Phase: I Cancer type: Unspecified Solid Tumor Therapy: vemurafenib + chemotherapy Variant class: BRAF mutation Country: United States

US State: TX

US Contact: MD Anderson [800-392-1611]

ALK fusion

NCT01634763 Other identifiers: CLDK378X1101, JapicCTI-121897, TrialTroveID-170968 A Phase I, Multicenter, Open-label Dose Escalation Study of LDK378, Population segments: ALK, Second line or greater/Refractory/Relapsed, Stage III, Administered Orally in Japanese Patients Stage IV with Tumors Characterized by Genetic Phase: Alterations in ALK I Cancer type: Melanoma Therapy: ceritinib

Variant class: ALK aberration Country: Japan

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 59 of 67

ALK fusion (continued)

NCT02186821 Other identifiers: 2014-0669, CLDK378AUS23, SIGNATURE, TrialTroveID-212790 Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Population segments: Aggressive, Classical, Diffuse large B-cell lymphoma (DLBCL), Activated Tumors: Module - 7 Ceritinib Follicular lymphoma (FL), Indolent, Mantle cell lymphoma (MCL), Nodular lymphocyte- (LDK378) for Patients Whose Tumors predominant, Second line or greater/Refractory/Relapsed, Stage III, Stage IV Have Aberrations in ALK or ROS1 Phase: II Cancer type: Unspecified Solid Tumor Therapy: ceritinib Variant class: ALK fusion Country: United States

US States: CO, IL, NM, OR, PA, RI, TX, WA

US Contact: Novartis Pharmaceuticals [888-669-6682]

NCT02034981 Other identifiers: AcSé, AcSé CRIZOTINIB, EudraCT Number: 2013-000885-13, AcSé CRIZOTINIB : Secured Access FSCA-crizotinib, TrialTroveID-200633, UC-0105/1303 to Crizotinib for Patients With Tumors Harboring a Genomic Alteration on One Population segments: Aggressive, Anaplastic, Follicular, Line of therapy N/A, of the Biological Targets of the Drug Medullary, Papillary, Pediatric or Adolescent, Peripheral T-cell lymphoma (PTCL), Stage III, Stage IV Cancer type: Unspecified Solid Tumor Phase: II Variant class: ALK aberration Therapy: crizotinib

Country: France

NCT00939770 Other identifiers: 10-C-0178, 100178, AAAE7196, ADV912, ADVL0912, COG- A Phase I/II Study of PF-02341066, ADVL0912, HUM00034160, PROFILE 912, TrialTroveID-112357 an Oral Small Molecule Inhibitor of Anaplastic Lymphoma Kinase (ALK) Population segments: (N/A), ALK, Indolent, Pediatric or Adolescent, Peripheral T-cell and c-Met, in Children With Relapsed/ lymphoma (PTCL), Second line or greater/Refractory/Relapsed Refractory Solid Tumors, Primary CNS Phase: Tumors, and Anaplastic Large Cell I/II Lymphoma Therapy: crizotinib Cancer type: Unspecified Solid Tumor Countries: Canada, United States Variant class: ALK fusion US States: AL, CA, CO, DC, GA, IL, IN, MA, MD, MI, MN, MO, NY, OH, OR, PA, TN, TX, WA, WI

US Contact: Multiple contacts: See www.clinicaltrials.gov for complete list of contacts.

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 60 of 67

ALK fusion (continued)

NCT02048488 Other identifiers: EudraCT Number: 2013-000686-37, PR-20-5006-C, REFMAL 290 A Phase I/IIa Open-Label, Dose IST, TrialTroveID-175362 Escalation and Cohort Expansion Trial of Oral TSR-011 in Patients With Advanced Population segments: Aggressive, ALK, Classical, First line, Indolent, Locally Solid Tumors and Lymphomas advanced, Metastatic, Nodular lymphocyte-predominant, Papillary, Second line or greater/Refractory/Relapsed, Stage II, Stage III, Stage IV Cancer type: Unspecified Solid Tumor Phase: I/II Variant class: ALK positive Therapy: TSR-011

Countries: Poland, Spain, Taiwan, United Kingdom, United States

US States: AZ, CA, TN, VA

US Contact: Clinical Trial Management Group [[email protected]]

No NCT ID - see other identifier(s) Other identifiers: ALKA-372-001, TrialTroveID-188328 A Phase I/II Dose Escalation Study of RXDX-101 in Patients with Solid Tumors Population segments: Adenocarcinoma, ALK, Line of therapy N/A, Stage II, Stage III, with Activating Alterations in the TrkA, Stage IV ROS1 or ALK Tyrosine Kinase Receptors Phase: I/II Cancer type: Unspecified Solid Tumor Therapy: entrectinib Variant class: ALK aberration Country: Italy

NCT02097810 Other identifiers: 14-131, 2014-0512, EudraCT Number: 2014-001326-15, A Phase I/IIa, Multicenter, Open-Label REec-2014-1210, RXDX-101-01, STARTRK-1, TrialTroveID-203930, UCI 14-01 Study of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Population segments: Second line or greater/Refractory/Relapsed, Stage III, Stage IV Cancer Confirmed to be Positive Phase: for TrkA, TrkB, TrkC, ROS1, or ALK I/II Molecular Alterations Study Targeting Therapy: ALK, ROS1 or TRKA/B/C (STARTRK-1) entrectinib Cancer type: Unspecified Solid Tumor Country: United States

Variant class: ALK aberration US States: CA, DC, FL, MA, NY, TN, TX

US Contact: Ignyta, Inc. [858-255-5959]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 61 of 67

ALK fusion (continued)

NCT02227940 Other identifiers: I 248813, NCI-2014-01766, TrialTroveID-215704 A Phase I Study of Ceritinib (LDK378), a Novel ALK Inhibitor, in Combination With Population segments: First line, Second line or greater/Refractory/Relapsed, Stage II, Gemcitabine-Based Chemotherapy in Stage III, Stage IV Patients With Advanced Solid Tumors Phase: I Cancer type: Unspecified Solid Tumor Therapy: ceritinib + chemotherapy Variant class: ALK fusion Country: United States

US State: NY

US Contact: Roswell Park [877-275-7724; [email protected]]

Cancer type: Unspecified Solid Tumor Phase: I Variant class: ALK fusion Therapy: crizotinib + dasatinib

Country: United States

US State: TX

US Contact: Dr. David S. Hong [800-392-1611]

NCT01548144 Other identifiers: 2011-1142, NCI-2012-00324, TrialTroveID-163762 A Two Steps Phase I Trial of Pazopanib or Pemetrexed in Combination With Population segments: Second line or greater/Refractory/Relapsed, Stage IV Crizotinib Followed by the Triplet, Phase: Crizotinib Plus Pazopanib Plus I Pemetrexed in Patients With Advanced Therapies: Malignancies crizotinib + pazopanib, crizotinib + pazopanib + pemetrexed, crizotinib + pemetrexed Cancer type: Unspecified Cancer Country: United States Variant class: ALK fusion US State: TX

US Contact: Dr Ralph Zinner [800-392-1611]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 62 of 67

ERBB2 amplification

NCT02091141 Other identifiers: 1403013519, 2014-0459, ML28897, ML28897PRO/02, My Pathway: An Open Label Phase TrialTroveID-205033 IIa Study Evaluating Trastuzumab/ Pertuzumab, Erlotinib, Vemurafenib, Population segments: Second line or greater/Refractory/Relapsed, Stage IV and Vismodegib in Patients Who Have Phase: Advanced Solid Tumors With Mutations II or Gene Expression Abnormalities Therapies: Predictive of Response to One of These erlotinib, pertuzumab + trastuzumab, vemurafenib, vismodegib Agents Country: United States Cancer type: Unspecified Solid Tumor US States: AR, AZ, CA, CT, FL, GA, IL, MD, ND, OH, OK, PA, SD, TN, TX, VA, WA Variant class: ERBB2 amplification US Contact: Reference Study ID Number: ML28897 [888-662-6728; [email protected]]

NCT01935843 Other identifiers: CHN-PLAGH-BT-009, TrialTroveID-193409 Clinical Study of Chimeric HER-2 Antigen Receptor-modified T Cells Population segments: HER2 positive, Second line or greater/Refractory/Relapsed, in Chemotherapy Refractory HER-2 Stage III, Stage IV Advanced Solid Tumors. Phase: I/II Cancer type: Unspecified Solid Tumor Therapy: CART-ERBB2 Variant class: ERBB2 positive Country: China

NCT01971515 Other identifiers: 2013-0525, CHRMS 14-081, EMR100018-001, TrialTroveID-196334 A Phase I, First-in-Human, Dose Escalation Trial of MSC2363318A, a Dual Population segments: Aggressive, Classical, EGFR, HER2 positive, Indolent, Nodular p70S6K/Akt Inhibitor, in Subjects With lymphocyte-predominant, Second line or greater/Refractory/Relapsed, Stage III, Stage Advanced Malignancies IV

Cancer type: Unspecified Solid Tumor Phase: I Variant class: ERBB2 aberration Therapy: MSC-2363318A

Country: United States

US States: CA, MN, TX, VT

US Contact: US Medical Information [888-275-7376]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 63 of 67

EGFR exon 19 deletion

NCT02091141 Other identifiers: 1403013519, 2014-0459, ML28897, ML28897PRO/02, My Pathway: An Open Label Phase TrialTroveID-205033 IIa Study Evaluating Trastuzumab/ Pertuzumab, Erlotinib, Vemurafenib, Population segments: Second line or greater/Refractory/Relapsed, Stage IV and Vismodegib in Patients Who Have Phase: Advanced Solid Tumors With Mutations II or Gene Expression Abnormalities Therapies: Predictive of Response to One of These erlotinib, pertuzumab + trastuzumab, vemurafenib, vismodegib Agents Country: United States Cancer type: Unspecified Solid Tumor US States: AR, AZ, CA, CT, FL, GA, IL, MD, ND, OH, OK, PA, SD, TN, TX, VA, WA Variant class: EGFR activating mutation US Contact: Reference Study ID Number: ML28897 [888-662-6728; [email protected]]

NCT02430727 Other identifiers: TrialTroveID-256701, XTPTC-309-96 The Safety and Efficacy Study of Afatinib (CT) Compared With Afatinib (GIOTRIF) Population segments: EGFR, Second line or greater/Refractory/Relapsed, Squamous in Patients With Solid Tumors (Including Cell, Stage III, Stage IV Mutations Identified EGFR) Phase: II Cancer type: Unspecified Solid Tumor Therapy: afatinib Variant class: EGFR mutation Country: Ukraine

NCT02189174 Other identifiers: 14-155, 14-282, CCLR457X2101, JapicCTI-152791, A Phase I/II Multicenter, Open-label TrialTroveID-212988 Study of CLR457, Administered Orally in Adult Patients With Advanced Solid Population segments: EGFR, First line, Second line or greater/Refractory/Relapsed, Malignancies. Stage III, Stage IV

Cancer type: Unspecified Solid Tumor Phase: I/II Variant class: EGFR mutation Therapy: CLR-457

Countries: Canada, Singapore, Spain, United States

US States: MA, NY, TN

US Contact: Novartis Pharmaceuticals [888-669-6682]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 64 of 67

EGFR exon 19 deletion (continued)

NCT02108964 Other identifiers: 14-112, 14-249, CEGF816X2101, EudraCT Number: A Phase I/II, Multicenter, Open-label 2013-004482-14, TrialTroveID-206746 Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients with Population segments: EGFR, Second line or greater/Refractory/Relapsed, Stage III, EGFRmut Solid Malignancies Stage IV

Cancer type: Unspecified Solid Tumor Phase: I/II Variant class: EGFR mutation Therapy: EGF-816

Countries: Canada, Germany, Japan, Republic of Korea, Singapore, Spain, Taiwan, United States

US States: MA, NY

US Contact: Novartis Pharmaceuticals [888-669-6682]

NCT01532011 Other identifiers: 2011-0916, TrialTroveID-162206 A Phase I Dose-Escalation Study of Erlotinib in Combination With Population segments: Second line or greater/Refractory/Relapsed, Stage III, Stage IV Pralatrexate in Subjects With Advanced Phase: Cancer I Cancer type: Unspecified Cancer Therapy: erlotinib + pralatrexate

Variant class: EGFR exon 19 deletion Country: United States

US State: TX

US Contact: Dr. Jennifer J. Wheler [713-745-9246]

No NCT ID - see other identifier(s) Other identifiers: 2010-813-00CH1, CTR20130972, TrialTroveID-132127 A Phase I First-in-Human, Safety, Efficacy and Tolerability Study of Population segments: CNS mets, EGFR, Second line or greater/Refractory/Relapsed, HMPL-813 for the Treatment of Various Stage IV Tumours Including Tumours Carrying Activating EGFR Mutations that Have Phase: I Metastasized to the Brain from Non- Small Cell Lung Cancer. Therapy: epitinib

Cancer type: Unspecified Cancer Country: China Variant class: EGFR activating mutation

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 65 of 67

EGFR exon 19 deletion (continued)

Cancer type: Unspecified Solid Tumor Phase: I Variant class: EGFR positive Therapy: MSC-2363318A

Country: United States

US States: CA, MN, TX, VT

US Contact: US Medical Information [888-275-7376]

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 66 of 67 Appendix: Evidence Summary by Variant Class

A variant class hierarchy was created to summarize gene variants with associated clinical evidence. Evidence items refers to citations across the different global data sources.

BRAF V600E mutation

Evidence Variant Class Items

BRAF mutation 16  BRAF exon 15 mutation 1  BRAF V600 mutation 37  BRAF V600E mutation 40  BRAF activating mutation 1  BRAF V600 mutation 37  BRAF V600E mutation 40

ALK fusion

Evidence Variant Class Items

ALK aberration 4  ALK positive 3  ALK fusion 9

ERBB2 amplification

Evidence Variant Class Items

ERBB2 aberration 1  ERBB2 positive 10  ERBB2 amplification 22

Lead Clinical Scientist: Keeda Snelson Senior BMS: Katherine Marquis Date: 07 Oct 2015 14:15:09 PM 67 of 67 Appendix: Evidence Summary by Variant Class (continued)

A variant class hierarchy was created to summarize gene variants with associated clinical evidence. Evidence items refers to citations across the different global data sources.

EGFR exon 19 deletion

Evidence Variant Class Items

EGFR positive 1  EGFR mutation 4  EGFR activating mutation 5  EGFRi sensitizing mutation 0  EGFR exon 19 deletion 12  EGFR exon 19 activating mutation 0  EGFR exon 19 deletion 12  EGFR exon 19 mutation 0  EGFR exon 19 activating mutation 0  EGFR exon 19 deletion 12

DISCLAIMER: The data presented here is a result of the curation of published data sources as of 2015.09(005), but may not be exhaustive. TEST DESCRIPTION

Oncofocus is a next-generation sequencing (NGS) based test that detects genomic alterations in ca ncer -related genes. Test results are intended to aid in patient management when used in conjunction with standard clinical as sessment. The test is neither intended nor validated for diagnosis.

35 19 23 HOTSPOT COPY NUMBER FUSION GENES VARIANTS DRIVERS

AKT1 FGFR3 MET ALK KRAS ABL1 FGFR3 ALK GNA11 M TOR AR MET AKT3 MET AR GN AQ NRAS BRAF M Y C ALK NTRK1 BRAF HRAS PDGFRA CCND1 M Y CN AXL NTRK2 CDK4 IDH1 PIK3 CA CDK4 PDGFRA BRAF NTRK3 C TNNB1 IDH2 RAF1 CDK6 PIK3 CA EGFR PDGFRA DDR2 JAK1 RET EGFR ERBB2 PPARG EGFR JAK2 ROS1 ERBB2 ERG RAF1 ERBB2 JAK3 SMO FGFR1 ETV1 RET ERBB3 KIT FGFR2 ETV4 ROS1 ERBB4 KRAS FGFR3 ETV5 ESR1 MAP2K1 FGFR4 FGFR1 FGFR2 MAP2K2 KI T FGFR2

CNV FUSION HO TSPO T HO TSPO T + FUSION HO TSPO T + CNV CN V + FUSION HO TSPO T + CN V + FUSION

Additional tests for targeted therapies available. Please visit www.oncologica.com/services TERMS AND CONDITIONS

Test Performance Oncologica tests are intended for clinical use. The tests’ performance characteristics were validated and verified under controlled conditions by Oncologica UK Ltd, which operates quality management systems based on ISO-15189:2012 standards to perform high complexity testing. The tests have not been cleared or approved by the United States Food and Drug Administration; however, such clearance or approval is not currently required.

Report Information compiled in this report is from publicly available sources. By updating the source database quarterly, Oncologica is making every effort to provide the most accurate and up-to-date information. However, accuracy and completeness are not guaranteed and test reports, once issued, will not be updated. Interpretation is performed by both specialist Consultant Histopathologists and by Oncologica's team of State Registered Biomedical and Clinical Scientists. Interpretation is for the specific requested test only.

No Guarantee By providing drug and clinical trial information for the reported diagnosis, Oncologica is not guaranteeing that any drug or clinical trial is necessarily appropriate for this patient. Healthcare providers should evaluate and interpret the information provided in this report, along with all other available clinical information about this patient, to determine the best treatment decisions in their own independent medical judgment. Patient management decisions should not be based on a single test, including this one, nor solely on the information contained in this report.

Alterations This test identifies genomic alterations found in the submitted tumor tissue to select cancer associated genes or portions of genes. While tested alterations were selected for inclusion in the test based on clinical level of evidence, Oncologica makes no claims regarding the clinical actionability of tested and reported alterations. Also note that this test only examines tumour, and not normal tissue from the patient, and therefore cannot distinguish between somatic and germline (i.e., heritable) alterations.

Drugs The drugs listed on the report are not ranked in any specific order as to predicted efficacy or appropriateness for this patient. Oncologica makes no guarantee or promise as to the effectiveness or suitability (or lack thereof) of any drug listed on this report. For more detailed information, healthcare providers should refer to the package insert for each FDA-approved drug listed in this report, and go to www.clinicaltrials.gov for information regarding drugs in clinical trials.

Reimbursement Oncologica makes no guarantee that any third party payer, including any governmental healthcare program, will pay for this test.