Adult Cancer Clinical Research Fast Facts – March 2021

BREAST STUDIES

Clinical Research Department: 407-303-2090

Research Coordinators Ingrid Acker, RN (407-303-4471) Alejandra Ricaurte RN (407-303-7346) [email protected] [email protected]

Ashley Young (407-303-7162) Lillie Danzy (407-303-2090) [email protected] [email protected]

Ext00000206: A Prospective Registry Study to Evaluate the Effect Ext00000206 of the DCISionRT™ Test on Treatment Decisions in Patients with ▪ DCIS Following Breast Conserving Therapy Diagnostic Registry DCIS ▪ Patient must be planning to undergo breast conserving surgery and eligible to receive radiation and/or systemic treatment

▪ Patient must have been diagnosed with DCIS within 120 days of

consent

▪ Patient must be greater than 25 years old

Target Accrual: 24 ▪ Exclusion: evidence of invasive breast cancer, including Actual Accrual: 20 microinvasion, lymph node involvement, or Paget’s disease of the nipple or suspicious mammogram findings in the lymph nodes or Orlando/Altamonte contralateral breast

EA1181 (CompassHER2-pCR): Preoperative THP and EA1181 postoperative HP in patients who achieve a pathologic complete ▪ response NeoAdjuvant Part 1 Component of: Her2 Positive The CompassHER2 Trials (COMprehensive use of Pathologic response ASSessment to optimize therapy in HER2-positive breast cancer)

▪ Must be HER2+, ER and PR can be positive or negative Target Accrual: 12 Actual Accrual: 0 ▪ Clinical Stage II and IIIa (T2-3/N0-2/M0): (cN0) are eligible if T size is > 2.0, (cN1-2) are eligible if T size is > 1.5.

▪ No prior hx of ipsilateral or contralateral invasive cancer: EXECPT

Hx of T1N0 triple negative breast cancer diagnosed 10 years earlier

are eligible

▪ No prior treatment for current breast cancer

Exclusion: T4 and/or N3 disease Orlando/Altamonte

A Randomized Phase III Trial Comparing Axillary Lymph Node Registration Step 2 (Confirmation of Dissection to Axillary Radiation in Breast Cancer Patients (cT1-3 Evaluability) will be temporarily Adult Cancer Clinical Research Fast Facts – March 2021

unavailable for new registrations, N1) Who Have Positive Sentinel Lymph Node Disease After effective 09/01/2020 Neoadjuvant Chemotherapy.

ALLIANCE A011202 ▪ Must Have ER, PR and HER2 status (by IHC and/or ISH) on ▪ diagnostic core biopsy prior to neoadjuvant therapy Status Post Neoadjuvant Chemotherapy ▪ Clinical Stage T1-N1 M0 breast cancer at Dx prior to start ▪ neoadjuvant chemotherapy Radiation ▪ Must have clinically negative axilla on physical examination at

completion of neoadjuvant therapy Target Accrual: 3 Actual Accrual:0 ▪ At least 4 cycles of neoadjuvant therapy prior to surgery

▪ Exclusion: Sandwich Chemo; neoadjuvant endocrine or radiation Orlando/Altamonte

SGNLVA-002 Single Arm, Open Label Phase 1b/2 Study of SGN-LIV1A in ▪ Combination with for First-Line Treatment of Triple Negative 1st Line Patients with Unresectable Locally-Advanced or Metastatic ▪ Triple-Negative Breast Cancer Unresectable Locally Advanced or Metastatic ▪ Participating in Part C Dose Level 1

On Hold

Orlando

A Phase III Randomized Trial of Hypofractionated Post ALLIANCE A221505 Mastectomy Radiation with Breast Reconstruction ▪ Post Mastectomy Radiation ▪ Stage IIa-IIIa; ECOG PS 0-1

▪ No prior radiation therapies Target Accrual: 5 Actual Accrual:23 ▪ Patients must be able to read and comprehend English

Orlando/Altamonte/Celebration

S1418: A Randomized, Phase III Trial to Evaluate the Efficacy and S1418 Safety of MK-3475 (Pembrolizumab) as Adjuvant Therapy for ▪ Triple Receptor-Negative Breast Cancer with >/= 1 CM Residual Adjuvant Invasive Cancer or Positive Lymph Nodes (ypN+) after Residual TNBC Neoadjuvant Chemotherapy

S1418 BAHO Substudy ▪ ER, PR and HER2 negative, as well as ER and PR <= 5% (BR006) is Temporarily positive or HER2 equivocal, breast cancers by ASCO/CAP closed to accrual, effective guidelines with > 1 cm residual invasive cancer in the breast, June 23, 2020. or any invasive tumor in the lymph nodes, including N1 mic, after completion of 16-24 weeks of neoadjuvant chemotherapy

Target Accrual: 4 (12 mths) ▪ Patients may receive post-operative chemotherapy for up to 24 weeks but must be registered for screening within 35 days of completion of adjuvant chemo (i.e. within 35 days of administration of last adjuvant chemotherapy Adult Cancer Clinical Research Fast Facts – March 2021

▪ Screening registration within 90 days after final breast surgery if no adjuvant chemo, and within 270 days if adjuvant chemo was given

▪ ER, PR and HER2 negative, as well as ER and PR <= 5% positive or HER2 equivocal, breast cancers by ASCO/CAP guidelines with > 1 cm residual invasive cancer in the breast, or any invasive tumor in the lymph nodes, including N1 mic, after completion of 16-24 weeks of neoadjuvant chemotherapy

▪ Patients may receive post-operative chemotherapy for up to 24 weeks but must be registered for screening within 35 days of completion of adjuvant chemo (i.e. within 35 days of administration of last adjuvant chemotherapy)

Orlando/Altamonte/Celebration ▪ Screening registration within 90 days after final breast surgery if no adjuvant chemo, and within 270 days if adjuvant chemo was given

Exclusion: No active autoimmune disease or Hep B,C, no prior immunotherapy or active immunosuppressive therapy, no live vaccines within 30 days of registration.

EA1131: A Randomized Phase III Post-Operative Trial of Platinum EA1131 Based Chemotherapy vs. Capecitabine in Patients with Residual ▪ Triple-Negative Breast Cancer following Neoadjuvant Adjuvant Chemotherapy Residual TNBC ▪ Clinical Stage II or III

▪ ER-, PR- criteria: < 10% cells stain positive, with weak intensity Actual Accrual: 10 score OR < 1% cells stain positive Target Accrual: 0 ▪ HER2- defined per ASCO/CAP guidelines

▪ Must have completed neoadjuvant taxane +/- anthracycline

▪ Must have completed definitive resection of primary tumor with negative margins. Patients with margins positive for LCIS are Open To Enrollment eligible

▪ Must found to have residual invasive cancer measuring > 1 cm and with more than minimal cellularity

▪ Radiotherapy may be given before or after protocol treatment per standard of care guildlines. Orlando/Altamonte ▪ Must have PAM50 anaylsis by digital mRNA quantitation on the FFPE block of residual disease

Exclusion: Must not have received cisplatin, carboplatin or capecitabine A Randomized, Double-Blind, Phase III Trial of BR004 Paclitaxel// with or ▪ Placebo in First-Line HER2-Positive Metastatic Breast Cancer Adult Cancer Clinical Research Fast Facts – March 2021

First Line Metastatic Her2 Positive ▪ Unresectable disease or metastatic disease

▪ Her-2 positive based on central testing

Actual Accrual: 1 ▪ Localize palliative radiation is allowed >14 days prior to Target Accrual: 4 randomization

Exclusion: Patients who receive a loading dose with a trastuzumab

biosimilar will not be eligible Orlando/Altamonte/Celebration

SGNTUC-016 --- Randomized, double-blind, phase 3 study of tucatinib or placebo in combination with ado- (T-DM1) for Metastatic subjects with unresectable locally-advanced or metastatic HER2+ HER2+ 1st or 2nd Line breast cancer

▪ Prior to randomization metastatic tumor tissue (archival or freshly obtained sample) must be submitted to the sponsor-designated

central laboratory for confirmatory HER2 testing

▪ Must have history of prior treatment with a taxane and trastuzumab in any setting, separately or in combination. Prior pertuzumab therapy is allowed, but not required

▪ Must have progression of unresectable LA/M breast cancer after Target Accrual: 5 last systemic therapy (as confirmed by investigator), or be Actual Accrual: 1 intolerant of last systemic therapy

Orlando ▪ Excludes prior treatment with T-DM1; tucatinib, , , , (DS-8201a), or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent.

A Randomized, Open Label, Phase III Trial to Evaluate the ALLIANCE AFT-38 (PATINA) Efficacy and Safety of Palbociclib + Anti-HER2 Therapy + ▪ Endocrine Therapy vs. Anti-HER2 Therapy + Endocrine 1st Line Metastatic Therapy after Induction Treatment for Hormone Receptor Her2 +/HR + Positive (HR+)/HER2-Positive Metastatic Breast Cancer

Target Accrual: 6 ▪ Histologically confirmed HER2+ and hormone receptor Actual Accrual: 2 positive (ER+ and/or PR+), metastatic breast cancer.

Study will close to enrollment on 3.05.2021

Orlando

Adult Cancer Clinical Research Fast Facts – March 2021

A Phase III Double-blind Randomised Study Assessing the D3615C00001 Efficacy and Safety of Capivasertib + Fulvestrant Versus Placebo + Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic Metastatic Hormone Receptor Positive, Human Epidermal Growth 1st, 2nd & 3rd line Factor Receptor 2 Negative (HR+/HER2−) Breast Cancer Following Recurrence or Progression On or After Treatment with an Aromatase Inhibitor (CAPItello-291) Target Accrual: ▪ Histologically confirmed HR+/HER2- breast cancer Accrual: 0 ▪ Patients are to have received treatment with an AI containing regimen (single agent or in combination) and have: o Radiological evidence of breast cancer recurrence or progression while on, or within 12 months of the end of (neo)adjuvant treatment with an AI, OR

o (b) Radiological evidence of progression while on prior AI administered as a treatment line for locally advanced or metastatic breast cancer (this does not need to be the most recent therapy

▪ Patients must have: o at least 1 lesion, not previously irradiated, that can be measured accurately at baseline as ≥10 mm in the longest diameter (except lymph nodes which must Orlando have short axis ≥15 mm) with CT or MRI which is suitable for accurate repeated measurements, OR o − in absence of measurable disease as defined above, at least 1 lytic or mixed (lytic + sclerotic) bone lesion that can be assessed by CT or MRI; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible

Exclusion: ▪ More than 2 lines of endocrine therapy for inoperable locally advanced or metastatic disease ▪ More than 1 line of chemotherapy for inoperable locally advanced or metastatic disease ▪ Prior treatment with Fulvestrant , other SERDs, PI3K, AKT and mTOR inhibitors

Adult Cancer Clinical Research Fast Facts – March 2021

EFC15935 EFC15935 A randomized, multicenter, double-blind phase 3 study of SAR439859 plus palbociclib versus letrozole plus palbociclib Metastatic for the treatment of patients with ER (+), HER2 (-) breast cancer 1st line who have not received any prior systemic anti-cancer treatment for advanced disease AMERRA-5

Target Accrual: ▪ ER+/HER2- loco-regional recurrent or metastatic disase not Actual Accrual: 0 amendable to radiation therapy or surgery in a curative intent

▪ Participants previously untreated with any systemic anti-cancer therapy for their loco-regional recurrent or metastatic disease

▪ At least 1 measurable lesion evaluable per RECIST 1.1, or non measurable bone only disease with at least 1 predominant lytic bone lesion without a measurable soft tissue component or Orlando/Altamonte/Celebration mixed lytic-blastic lesioin without a measurable soft tissue component must be present

▪ It is recommended that men with no prior bilateral orchiectomy and pre/perimenopausal women are on a GnRH agonist for at least 4 weeks prior to randomization. Exclusion: ▪ Disease recurrence while on, or within 12 months of completion of (neo)adjuvant endocrine therapy with any of the following agents: (criterion modified by amendment 03) - Aromatase inhibitor - eg, letrozole, anastrozole, exemestane; - Selective estrogen receptor modulator - eg, tamoxifen, toremifene, raloxifene - CDK4/6 inhibitors - eg, palbociclib, ribociclib, abemaciclib A Phase I/II Open-label, First-in-Human, Multicenter, Dose, OP-1250-001 Escalation and Dose Expansion Study Of OP-1250 as a single agent in combination with a CDK4/6 inhibitor and a PI3kα (AHCI is participating in both inhibitor in adult subjects with advanced and/or metastatic Phase I & II portion) Hormone Receptor (HR+)positive, HER2(-)negative breast cancer • Tumor must be ER positive and HER-2 negative as determined in the most recently obtained archival tumor tissue sample Actual Accrual: 4 • The subject must have received at least one (1) prior hormonal regimens for locally advanced or metastatic disease

• Subjects must have progressed following at least six (6) months

of a prior continuous endocrine therapy for locally advanced or

metastatic breast cancer. (Progression during adjuvant hormonal therapy or within twelve (12) months of stopping adjuvant Orlando hormonal therapy will be considered a metastatic regimen for the purposes of this study.)

ALL SOLID TUMORS OTHER THAN NSCLC Research Coordinators Rosangela Spear 407-303-2090 Corina Mattix, RN 407-303-1327 [email protected] Corina. [email protected]

Adult Cancer Clinical Research Fast Facts – March 2021

VLS-101-003 Minimal required prior therapy for subjects with breast cancer: a. ER- and PR-negative; HER2-negative disease (TNBC):≥1 cytotoxic therapy for metastatic disease b. ER- and PR-negative; HER2-positive disease: ≥2 HER-2-targeted therapies for metastatic disease c. ER- and/or PR-positive; HER2-positive disease: ≥2 HER-2-targeted therapies for metastatic disease d. ER- and/or PR-positive; HER2-negative disease: ≥1 hormonal therapy; ≥1 cyclin-dependent kinase 4/6 inhibitor (CDK4/6i); and ≥1 cytotoxic therapy for metastatic disease Minimal required prior therapy for subjects with non-squamous NSCLC: a. Disease positive for EGFR-sensitizing-mutation, ALK rearrangement, ROS1 rearrangement, BRAF-V600E mutation, NTRK gene fusion, MET exon 14 skipping mutation, or RET rearrangement: ≥1 relevant inhibitor and ≥1 platinum-containing regimen b. Disease negative for EGFR-sensitizing-mutation, ALK rearrangement, ROS1 rearrangement, BRAF-V600E mutation, NTRK gene fusion, MET exon 14 skipping mutation, RET rearrangement: ≥1 therapy including a checkpoint inhibitor and ≥1 platinum-containing regimen Note: Subjects with squamous cell NSCLC will not be enrolled.

APL-101-01 APL-101-01: Phase 1 / 2 Multicenter Study of the Safety, 1st line or 2nd Line Pharmacokinetics, and Preliminary Efficacy of APL-101 in Subjects ▪ with Non-Small Cell Lung Cancer with c-Met EXON 14 skip Advanced/Metastatic mutations and c-Met Dysregulation Advance Solid Tumors

Cohort A: EXON 14 Non-Small-Cell Lung Cancer – c-Met inhibitor naïve Phase 2 Participation ▪ Histologically or cytologically confirmed NSCLC with EXON 14 skip mutations

▪ All histologies, including pulmonary sarcomatoid carcinoma and squamous

▪ Unresectable or metastatic disease (Stage 3b/4)

▪ Pretreated subject’s refractory to or intolerable to standard therapies (if available, must include anti-PD-1/PD-L1 based systemic therapy) with no more than three lines of prior therapy

▪ Not received any c-Met inhibitor (e.g., , , , etc.)

Cohort B: EXON 14 Non-Small-Cell Lung Cancer – c-Met inhibitor experienced

▪ Histologically or cytologically confirmed NSCLC with EXON 14 skip mutations

▪ All histologies, including pulmonary sarcomatoid carcinoma and squamous

▪ Unresectable or metastatic disease (Stage 3b/4) Adult Cancer Clinical Research Fast Facts – March 2021

▪ Refractory to standard therapies with no more than three prior lines of therapy

▪ Radiographic progression on any c-Met inhibitor (e.g., crizotinib, capmatinib, savolitinib, etc.) at any point in the past

Cohort C: Basket Tumor Types (c-Met high-level amplifications)

▪ Any tumor type regardless of histology, including relapsed/refractory NSCLC, excluding NSCLC EXON 14 skip mutation, that meets inclusion criteria c-Met high-level amplification A PHASE 1/2, OPEN-LABEL, MULTICENTER STUDY TO 16-214-05 INVESTIGATE THE SAFETY AND PRELIMINARY EFFICACY OF NKTR-214 IN COMBINATION WITH PEMBROLIZUMAB IN PATIENTS NSCLC, Hepatocellular, WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS , Urothelial, Dose Optimization Cohorts (Cohorts 1a and 1b) Head and Neck ▪ 1L and 2L Melanoma a. Histologically confirmed stage III (unresectable) No Slots as of 2/11/21 or stage IV (metastatic) melanoma

▪ 1L and 2L Non-small Cell Lung Cancer (NSCLC) a. Histologically confirmed or cytologically confirmed diagnosis of stage IV NSCLC ▪ Patients with epidermal receptor (EGFR), c-ros oncogene 1 (ROS1), BRAF v600e, or anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression following approved targeted therapy as applicable for these aberrations

▪ 1L and 2L Urothelial Carcinoma Histologically or cytologically documented locally advanced or metastatic urothelial carcinoma

▪ 1L and 2L Head and Neck Squamous Cell Carcinoma (HNSCC) Histologically confirmed diagnosis of recurrent and unresectable or metastatic HNSCC

▪ 1L and 2L Hepatocellular Carcinoma (HCC) Histologically confirmed diagnosis of locally advanced or metastatic HCC

Dose Expansion (Cohort 2)

▪ 1L Non-Small Cell Lung Cancer (Cohorts 2.1, 2.2, and 2.3) Histologically or cytologically confirmed diagnosis of stage IV NSCLC

Adult Cancer Clinical Research Fast Facts – March 2021

A Phase 2 Study of Seribantumab in Adult Patients with - ELVACAP-001-01 1 (NRG1) Fusion Positive Locally Advanced or Metastatic Solid (NRG1 fusion Positive) Tumors CRESTONE ▪ ▪ Patients must have received a minimum of one prior standard therapy 2nd line beyond appropriate for their tumor type and stage of disease ▪ NRG1 gene fusion identified through molecular assays ▪ ▪ ECOG 0-2 Advanced/ Metastatic ▪ Measurable disease per RECIST ▪ Excluded if patient has symptomatic or untreated brain metastases. Received anticancer therapy within 28 days prior to planned start of seribantumab or 5 half-lives, whichever is shorter

Pending Studies A011801: The CompassHER2 Trials (Comprehensive Use of Pathologic Response Assessment to Optimize Therapy in HER2-Positive Breast Cancer) CompassHER2 Residual Disease (RD), a Double- Blinded, Phase III Randomized Trial of T-DM1 Compared With T-DM1 and Tucatinib