NEUER REPORT AB NOVEMBER FoundationOne®CDx-Report: Jetzt mit EU- zugelassenen Therapien und verbesserter Darstellung Seite 1: Schneller, übersichtlicher Zugriff auf die Informationen, die Sie benötigen.1

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1 Prädiktive Biomarker. 3 Relevante negative Ergebnisse. 5 Klinische Studien. Relevante Angaben zu TMB- und MSI- Schließt wichtige Alterationen Studien, für die Ihr Patient / Status, die unterstützen können, aus, die nicht entdeckt wurden Ihre Patientin basierend auf das Ansprechen auf eine seinem / ihrem Tumorprofil Immuntherapie zu beurteilen 4 Therapien mit potentiell geeignet sein könnte klinischem Nutzen. Therapien, 2 Genetische Alterationen. die in der EU* für die genetischen 6 Genetische Alterationen ohne Klinisch relevante Alterationen Alterationen Ihres Patienten / zugehörige Behandlungsoptionen. in > 300 getesteten, krebs­ Ihrer Patientin zugelassen sind Damit Sie Unklarheiten aus­ relevanten Genen räumen und das bestmögliche Vorgehen bestimmen können

*Die in diesem Report gelisteten Therapien können durch ein zentralisiertes Verfahren der EU oder ein nationales Prozedere in einem EU-Mitgliedsstaat zugelassen worden sein. MSI, Microsatelliteninstabilität. TMB, Tumormutationslast (tumour mutational burden). Seite 2 und folgende: Detaillierte weiterführende und unterstützende Informationen

PATIENT TUMOR TYPE REPORT DATE PATIENT TUMOR TYPE REPORT DATE PATIENT TUMOR TYPE REPORT DATE Sample, Jane Lung adenocarcinoma 01 Jan 2018 Sample, Jane Lung adenocarcinoma 01 Jan 2018 Sample, Jane Lung adenocarcinoma 01 Jan 2018

GENOMIC SIGNATURES THERAPIES APPROVED IN THE EU IN PATIENT'S TUMOR TYPE THERAPIES APPROVED IN THE EU IN PATIENT'S TUMOR TYPE PRF# XXXXXXXX PRF# XXXXXXXX PRF# XXXXXXXX

GENOMIC SIGNATURE partial responses following treatment with TMB14,68,69,70. A large study of Chinese patients pembrolizumab 74 or nivolumab75, a patient with with lung adenocarcinoma reported a shorter Afatinib AREAS OF THERAPEUTIC USE (DCR) (51% vs. 40%) for patients treated with afatinib (Soria Erlotinib AREAS OF THERAPEUTIC USE BR.21 Phase 3 randomized trial demonstrating prolonged Tumor Mutational hypermutant glioblastoma who obtained clinical median overall survival (OS) for tumors with a Afatinib is an irreversible kinase inhibitor that targets the et al., 2015; 26156651). Phase 2/3 studies of afatinib Erlotinib is an EGFR �rosine kinase inhibitor and available overall survival for unselected patients with NSCLC treated Burden benefit from pembrolizumab76, and two pediatric higher number of mutations in a limited gene set Assay findings associations kinase domains of EGFR, ERBB2/HER2, and ERBB4. It is treatment for patients with erlotinib- or gefitinib-resistant Assay findings associations in the EU for the treatment of advanced non-small cell lung with erlotinib compared with standard chemotherapy patients with biallelic mismatch repair deficiency compared with lower mutational number (48.4 vs. available in the EU to treat patients with advanced NSCLC have generally reported partial responses (PRs) of cancer (NSCLC) as first-line therapy or switch maintenance (Shepherd et al., 2005; 16014882). Furthermore, several CATEGORY (bMMRD)-associated ultrahypermutant 61.0 months)66. EGFR squamous non-small cell lung cancer following progression only 7-9% (Miller et al., 2012; 22452896, Chen et al., 2013; EGFR therapy for patients with EGFR-activating mutations and randomized Phase 3 trials have shown a significant TMB-Intermediate (11 Muts/Mb) glioblastoma who experienced clinically and amplification, L858R on prior therapy or with advanced non-small cell lung 23664448, Katakami et al., 2013; 23816963, Landi et al., 2014; amplification, L858R as second-line therapy for patients who have progressed improvement in response and progression-free survival for radiologically significant responses to nivolumab77. FINDING SUMMARY cancer (NSCLC) positive for activating EGFR mutations. 25242668, De Greve et al., 2015; 25682316, Yang et al., 2015; on prior chemotherapy. Erlotinib is also available in erlotinib compared with combination chemotherapy in In patients with melanoma, mutational load was Tumor mutational burden (TMB, also known as 26051236), and DCRs of more than 50% (De Greve et al., combination with gemcitabine to treat metastatic patients with known EGFR mutations. �is includes the associated with long-term clinical benefit from mutational load) is a measure of the number of GENE ASSOCIATION 2015; 25682316); in particular, disease control was achieved pancreatic cancer. EURTAC trial of erlotinib versus platinum-based POTENTIAL TREATMENT STRATEGIES ipilimumab64,78 and anti-PD-1/anti-PD-L1 somatic protein-coding base substitution and EGFR activating mutations or amplification may indicate for 2/2 patients with EGFR-amplified NSCLC (De Greve et chemotherapy as first-line treatments (Rosell et al., 2011; On the basis of emerging clinical evidence, treatments71. For patients with metastatic insertion/deletion mutations occurring in a tumor sensitivi� to afatinib. In Phase 2 studies of afatinib, patients al., 2015; 25682316) and 9/14 patients with T790M-positive GENE ASSOCIATION 22285168) and the SATURN trial of erlotinib as maintenance increased TMB may be associated with greater urothelial carcinoma, those who responded to specimen. TMB is affected by a varie� of causes, with EGFR-amplified NSCLC achieved an objective NSCLC (Yang et al., 2015; 26051236). �e T790M mutation Amplification or activation of EGFR may predict sensitivi� therapy following first-line platinum-based chemotherapy sensitivi� to immunotherapeutic agents, atezolizumab treatment had a significantly including exposure to mutagens such as ultraviolet response rate of 20% (5/25) and a disease-control rate of has been implicated in reduced response to afatinib (Wu et to therapies such as erlotinib. In a prospective study of (Cappuzzo et al., 2010; 20493771). On the other hand, the including anti-CTLA-464, anti-PD- L163,71,72, increased mutational load [12.4 mutations (muts) light in melanoma54,55 and cigare�e smoke in lung 64% (16/25) (Cappuzzo et al., 2015; 25514804), and 2/5 al., 2016; 26862733, Landi et al., 2014; 25242668, Kim et al., advanced NSCLC treated with gefitinib (n=102), EGFR copy efficacy of erlotinib for patients lacking the common EGFR and anti-PD-1 therapies57,65,73; such as per megabase (Mb)] compared to nonresponders cancer56,57, mutations in the proofreading patients with EGFR amplification in other solid tumors 2012; 22228822), with a secondary T790M mutation gain was significantly associated with improved survival activating alterations (exon 19 deletion or L858R mutation) ipilimumab, atezolizumab, avelumab, durvalumab, (6.4 muts/Mb)63, and mutational load of 16 muts/ domains of DNA polymerases encoded by the experienced stable disease (Kwak et al., 2013; 23775486). reported in 48% (20/42) of patients with afatinib-resistant [hazard ratio (HR)=0.44] (Cappuzzo et al., 2005; 15870435). may be regimen-dependent. For patients with NSCLC and pembrolizumab, and nivolumab. In multiple solid Mb or higher was associated with significantly POLE and POLD1 genes58,59,60,61,62, and lung adenocarcinoma (Wu et al., 2016; 26862733). �e Several meta-analyses spanning 14 to 20 studies of patients wild-�pe EGFR, chemotherapy was found to be more tumor �pes, higher mutational burden has longer overall survival72. microsatellite instabili� (MSI)58,61,62. �e tumor SUPPORTING DATA combination of afatinib with cetuximab resulted in a higher with advanced NSCLC receiving single-agent erlotinib or effective than erlotinib as first-, second-, or third-line corresponded with response and improved seen here harbors an intermediate TMB. �is level Phase 3 clinical trials have demonstrated that treatment response rate (29%) for patients with erlotinib- or gefitinib- gefitinib (n=1725 to 1854) reported the association of treatment (Garassino et al., 2013; 23883922, Kawaguchi et al., prognosis. Pembrolizumab improved progression- FREQUENCY & PROGNOSIS of TMB is high enough that it may be associated with afatinib, compared to chemotherapy, leads to resistant disease (Janjigian et al., 2014; 25074459), including increased EGFR copy number with improved overall 2014; 24841974, Liu et al., 2016; 26206590). However, as free survival (14.5 vs. 3.4-3.7 months) in patients Intermediate TMB has been reported in 30-31% of with sensitivi� to immune checkpoint inhibitors significantly increased progression-free survival for patients T790M-positive cases (Janjigian et al., 2014; 25074459, survival (HR=0.72 to 0.77), although the survival benefit was maintenance therapy, erlotinib reduced risk for progression with non-small cell lung cancer (NSCLC) and non-small cell lung carcinomas (NSCLC), including in some tumor �pes, including anti-PD-1 therapy with EGFR-mutant NSCLC (Sequist et al., 2013; 23816960, Ribeiro Gomes and Cruz, 2015; 26056478), although adverse not observed for East Asian populations (HR=0.79 to 1.11) compared with placebo by 19% (hazard ratio = 0.81) (Liu et higher mutational load (greater than 200 30% of adenocarcinomas and 41% of squamous cell in non-small cell lung cancer57, anti-PD-L1 therapy Wu et al., 2014; 24439929), and increased overall survival reactions may be a concern with this combination (Zhang et al., 2017; 27664271, Dahabreh et al., 2011; al., 2016; 26206590). �e single-arm, Phase IV TRUST trial nonsynonymous mutations; hazard ratio = 0.19)57. carcinomas (SCC) (Spigel et al., 2016; ASCO in bladder cancer63, and anti-CTLA-4 therapy in (OS) for patients with EGFR exon 19 alterations specifically (Castellanos et al., 2015; 25842367). Upon progression on 20826716, Dahabreh et al., 2010; 20028749). 100 for genomically unselected patients with advanced NSCLC In studies of patients with either NSCLC or Abstract 9017). Intermediate TMB was frequently melanoma64, potentially due to expression of (Yang et al., 2015; 25589191). A Phase 3 trial comparing afatinib, �rther benefit has been reported from combination who failed on, or were unsuitable for, chemotherapy or who colorectal cancer (CRC), patients whose tumors observed in NSCLC with BRAF (31%) or KRAS immune-reactive neo-antigens in these tumors57. afatinib with erlotinib as second-line therapies for advanced treatment with afatinib and paclitaxel (Schuler et al., 2016; SUPPORTING DATA were ineligible for erlotinib clinical trials reported a disease harbor elevated mutational burden reported higher (39%) mutation (Spigel et al., 2016; ASCO Abstract However, in other studies of checkpoint inhibitors, lung squamous cell carcinoma reported significantly higher 26646759). �e initial approval of erlotinib in NSCLC was based on the control rate of 69% (Reck et al., 2010; 20736854). overall response rates to pembrolizumab57,65,73. 9017). Although some studies have reported a lack including anti-PD-1 therapy in colorectal cancer65, OS (7.9 months vs. 6.8 months) and disease control rate Anti-PD-1 therapies have achieved clinical of association between smoking and mutational patients with tumors harboring intermediate TMB benefit for certain patients with high mutational burden in NSCLC (Schwartz et al., 2016; ASCO levels experienced lower rates of clinical benefit burden, including 3 patients with endometrial Abstract 8533)66,67, several other large studies did than those with high TMB. Gefitinib AREAS OF THERAPEUTIC USE free survival (PFS) in a subgroup of patients with EGFR adenocarcinoma who reported sustained find a strong association with increased Osimertinib AREAS OF THERAPEUTIC USE EGFR T790M-positive advanced NSCLC who had Gefitinib is an EGFR �rosine kinase inhibitor and available mutation-positive NSCLC as compared with carboplatin/ Osimertinib is an irreversible EGFR �rosine kinase progressed on EGFR TKI therapy, osimertinib compared Assay findings associations in the EU to treat advanced non-small cell lung cancer paclitaxel doublet chemotherapy (hazard ratio for inhibitor (TKI) that is selective for EGFR TKI-sensitizing with combination platinum therapy led to longer median (NSCLC) with activating EGFR mutations. progression = 0.48) (Fukuoka et al., 2011; 21670455, Mok et Pembrolizumab therapy resulted in a significantly FINDING SUMMARY Assay findings associations GENOMIC SIGNATURE mutations and the EGFR T790M mutation. It is available in progression-free survival (PFS) (10.1 months vs. 4.4 months), al., 2009; 19692680). In a Phase 2 study, addition of lower objective response rate (ORR) in MSS Microsatellite instabili� (MSI) is a condition of EGFR the EU to treat patients with advanced EGFR T790M- including for patients with metastases to the central nervous GENE ASSOCIATION pemetrexed to gefitinib improved median PFS (15.8 months) Microsatellite status colorectal cancer (CRC) compared with MSI-H CRC genetic hypermutabili� that generates excessive EGFR amplification, L858R positive non-small cell lung cancer (NSCLC). system (8.5 months vs. 4.2 months). An objective response Amplification or activation of EGFR may predict sensitivi� compared to treatment with gefitinib alone (10.9 months) in (0% vs. 40%)65. Similarly, a clinical study of amounts of short insertion/deletion mutations in L858R CATEGORY rate (ORR) of 71% was achieved with osimertinib compared to therapies such as gefitinib. Clinical studies have East Asian patients with treatment-naïve, advanced non- nivolumab, alone or in combination with the genome; it generally occurs at microsatellite GENE ASSOCIATION to 31% with combination platinum therapy (Mok et al., 2016; consistently shown significant improvement in response squamous NSCLC and activating EGFR mutations (Cheng et MS-Stable ipilimumab, in patients with CRC reported a DNA sequences and is caused by a deficiency in EGFR TKI-sensitizing mutations and/or the EGFR T790M DOI: 10.1056/NEJMoa1612674). A Phase 2 study of rates and progression-free survival for patients with EGFR- al., 2016; 27507876). A retrospective analysis of patients significantly higher response rate in patients with DNA mismatch repair (MMR) in the tumor127. mutation may predict sensitivi� to osimertinib22,179. osimertinib reported an ORR of 70% with a median mutated NSCLC treated with gefitinib, compared to with advanced NSCLC of Asian descent receiving first-line MSI-H tumors than those without (Overman et al., Defective MMR and consequent MSI occur as a T790M-positive patients showed higher response rates than duration of response of 11.4 months and a median PFS of chemotherapy (Han et al., 2012; 22370314, Maemondo et al., gefitinib therapy reported that patients with EGFR exon 19 2016; ASCO Abstract 3501). result of genetic or epigenetic inactivation of one of T790M- negative cases in a Phase 1 study for patients with 9.9 months for T790M-positive NSCLC patients with 2010; 20573926, Mitsudomi et al., 2010; 20022809, Mok et mutations experienced longer median PFS (10.9 months) the MMR pathway proteins, primarily MLH1, acquired EGFR TKI resistance (61% vs. 21%)22. Although disease progression a�er previous EGFR TKI therapy180. A al., 2009; 19692680, Petrelli et al., 2011; 22056888, Qi et al., compared to patients with EGFR mutations in exons 18 (7.9 POTENTIAL TREATMENT STRATEGIES FREQUENCY & PROGNOSIS MSH2, MSH6, or PMS2127,128,129. �e tumor seen tumors with EGFR amplification may not be sensitive to Phase 1 trial demonstrated similar outcomes for T790M- 2015; 25329826, Zhao et al., 2015; 25546556). months), 20 (1.2 months), 21 (7.7 months), or double On the basis of clinical evidence, MSS tumors are MSI-high (MSI-H) has been reported at various here is microsatellite-stable (MSS), equivalent to osimertinib, which selectively targets mutated EGFR, positive patients (Yang et al., 2016; ELCC Abstract mutations (5.7 months); however, no differences in overall significantly less likely than MSI-H tumors to frequencies in non-small cell lung cancer (NSCLC) the clinical definition of an MSS tumor: one with preclinical data indicate sensitivi� of various activating LBA2_PR), but reported an ORR of 21% and median PFS of SUPPORTING DATA survival were seen between EGFR mutations (Sutiman et al., respond to anti-PD-1 immune checkpoint as well as in small cell lung mutations in none of the tested microsatellite EGFR alterations to osimertinib.179 2.8 months for T790M-negative cases with acquired EGFR Gefitinib achieved an objective response rate of 69.8% and 2017; 27908825). In a Phase 1 study for treatment-naïve inhibitors139,140,141, including approved therapies cancer133,134,135,136,137,138. One study observed markers130,131,132. MSS status indicates MMR TKI resistance22. Treatment-naïve patients with EGFR- an overall survival of 19.2 months as first-line treatment of patients with NSCLC, best objective response rates of 78% nivolumab and pembrolizumab (Overman et al., MSI-H in 0.8% (4/480) of lung adenocarcinoma proficiency and �pically correlates with intact SUPPORTING DATA mutated NSCLC achieved an ORR of 77% (46/60 overall, Caucasian patients with non-small cell lung carcinoma (7/9) were observed in patients treated with combination 2016; ASCO Abstract 3501)65. In a retrospective cases; the MSI-H tumors occurred in patients with expression of all MMR family Osimertinib has been studied primarily for the treatment of 20/30 with 80 mg, 26/30 with 160 mg), a stable disease rate (NSCLC) and EGFR sensitizing mutations, which were gefitinib and the PD-L1 inhibitor durvalumab as first-line analysis of 361 patients with solid tumors treated smoking history, and 3/4 MSI-H cases had proteins127,129,131,132. EGFR-mutated NSCLC. In Phase 3 study for patients with of 20% (12/60), and a median PFS of 19.3 months mostly EGFR exon 19 deletions and EGFR L858R (Douillard treatment and of 80% (8/10) in those treated with the with pembrolizumab, 3% were MSI-H and nonsynchronous carcinomas in other organs, et al., 2014; 24263064). In the retrospective analysis of a combination subsequent to gefitinib monotherapy (Gibbons experienced a significantly higher ORR compared although none of the patients were diagnosed with Phase 3 study in East Asia, gefitinib increased progression- et al., 2016; 27198414). with non-MSI-H cases (70% vs. 12%, p=0.001) Lynch syndrome133. (Ayers et al., ASCO-SITC 2016; Abstract P60).

Electronically Signed by Jane Doctor, M.D., Ph.D. • Elizabeth Doctor, M.D., Medical Director • 15 January 2018 Sample Preparation: Nonnenwald 2, 82377 Penzberg, Germany Electronically Signed by Jane Doctor, M.D., Ph.D. • Elizabeth Doctor, M.D., Medical Director • 15 January 2018 Sample Preparation: Nonnenwald 2, 82377 Penzberg, Germany Electronically Signed by Sample Preparation: Nonnenwald 2, 82377 Penzberg, Germany Foundation Medicine, Inc. • +49 7624 14 2098 Sample Analysis: Nonnenwald 2, 82377 Penzberg, Germany Foundation Medicine, Inc. • +49 7624 14 2098 Sample Analysis: Nonnenwald 2, 82377 Penzberg, Germany Foundation Medicine, Inc. • +49 7624 14 2098 Sample Analysis: Nonnenwald 2, 82377 Penzberg, Germany PAGE 3 of 22 PAGE 7 of 22 PAGE 8 of 19

Liefert wichtige Hintergrund­ informationen zu genetischen Bietet Evidenz-basierte Erkenntnisse zu den Therapien, Alterationen im Tumor Ihrer die zum Profil Ihres Patienten / Ihrer Patientin passen, Patienten, insbesondere zur Evidenz sowohl bei der untersuchten als auch weiteren Tumorarten. zu den assoziierten potentiellen Behandlungsstrategien.

PATIENT TUMOR TYPE REPORT DATE PATIENT TUMOR TYPE REPORT DATE PATIENT TUMOR TYPE REPORT DATE Sample, Jane Lung adenocarcinoma 01 Jan 2018 Sample, Jane Lung adenocarcinoma 01 Jan 2018 Sample, Jane Lung adenocarcinoma 01 Jan 2018

CLINICAL TRIALS APPENDIX Variants of Unknown Significance APPENDIX Genes assayed in FoundationOne®CDx PRF# XXXXXXXX PRF# XXXXXXXX PRF# XXXXXXXX

IMPORTANT Clinical trials are ordered by gene and contained below, the information available in the public clinical trial enrollment criteria For additional information NOTE One or more variants of unknown significance (VUS) were detected in this patient's tumor. �ese variants may not have been adequately characterized FoundationOne CDx is designed to include genes known to be somatically altered in human solid tumors that are validated targets for therapy, either prioritized in the following descending order: Pediatric domain is continually updated and should be investigated about listed clinical trials or to conduct a search for in the scientific literature at the time this report was issued, and/or the genomic context of these alterations makes their significance unclear. We choose to approved or in clinical trials, and/or that are unambiguous drivers of oncogenesis based on current knowledge. �e current assay interrogates 324 genes as trial qualification → Geographical proximi� → Trial phase → by the physician or research staff. �e clinical trials listed additional trials, please see clinicaltrials.gov or local include them here in the event that they become clinically meaning�l in the �ture. well as introns of 28 genes involved in rearrangements. �e assay will be updated periodically to reflect new knowledge about cancer biology Trial verification within last 2 months. While every effort in this report may not be complete and exhaustive or may registries in your region. is made to ensure the accuracy of the information include trials for which the patient does not meet the DNA GENE LIST: ENTIRE CODING SEQUENCE FOR THE DETECTION OF BASE SUBSTITUTIONS, INSERTION/DELETIONS, AKT3 EP300 IRS2 LRP1B AND COPY NUMBER ALTERATIONS GENOMIC SIGNATURE RATIONALE E132D S12L, S24L, and S26F M543L and R1286Q C1199F ABL1 ACVR1B AKT1 AKT2 AKT3 ALK ALOX12B ATRX AMER1 (FAM123B) Increased tumor mutational burden may predict terms such as “PD-L1", “B7-H1", “PD-1", Tumor Mutational APC AR ARAF ARFRP1 ARID1A ASXL1 ATM ATR AURKA response to anti-PD-1 and anti-PD-L1 immune “pembrolizumab", “nivolumab", “atezolizumab", AURKB AXIN1 AXL BAP1 BARD1 BCL2 BCL2L1 BCL2L2 BCL6 Burden checkpoint inhibitors. Examples of clinical trials “MPDL3280A", “durvalumab", “MEDI4736", that may be appropriate for this patient are listed “avelumab", “MSB0010718C", “BMS-936559", BCOR BCORL1 BRAF BRCA1 BRCA2 BRD4 BRIP1 BTG1 BTG2 CATEGORY below. �ese trials were identified through a search “pidilizumab", “CT-011", “NSCLC", “lung", “solid BTK C11orf30 (EMSY) C17orf39 (GID4) CALR CARD11 CASP8 CBFB CBL CCND1 TMB-Intermediate (11 Muts/Mb) of the trial website clinicaltrials.gov using keyword tumor", and/or “advanced cancer". CCND2 CCND3 CCNE1 CD22 CD274 (PD-L1) CD70 CD79A CD79B CDC73 CDH1 CDK12 CDK4 CDK6 CDK8 CDKN1A CDKN1B CDKN2A CDKN2B CDKN2C CEBPA CHEK1 CHEK2 CIC CREBBP CRKL CSF1R CSF3R NCT01714739 PHASE 1 / PHASE 2 CTCF CTNNA1 CTNNB1 CUL3 CUL4A CXCR4 CYP17A1 DAXX DDR1 DDR2 DIS3 DNMT3A DOT1L EED EGFR EP300 EPHA3 EPHB1 A Phase 1/2 Study of the Combination of Lirilumab (Anti-KIR) Plus Nivolumab (Anti-PD-1) or Lirilumab TARGETS EPHB4 ERBB2 ERBB3 ERBB4 ERCC4 ERG ERRFI1 ESR1 EZH2 Plus Nivolumab and Ipilimumab in Advanced Refractory Solid Tumors CTLA-4, KIR, PD-1 FAM46C FANCA FANCC FANCG FANCL FAS FBXW7 FGF10 FGF12 FGF14 FGF19 FGF23 FGF3 FGF4 FGF6 FGFR1 FGFR2 FGFR3 LOCATIONS: Madrid (Spain), Paris (France), Barcelona (Spain), New York, Toronto (Canada), Illinois, Oregon, Pennsylvania, Ohio, Tennessee, Lyon Cedex 08 (France) FGFR4 FH FLCN FLT1 FLT3 FOXL2 FUBP1 GABRA6 GATA3 GATA4 GATA6 GNA11 GNA13 GNAQ GNAS GRM3 GSK3B H3F3A HDAC1 HGF HNF1A HRAS HSD3B1 ID3 IDH1 IDH2 IGF1R NCT02486718 PHASE 3 IKBKE IKZF1 INPP4B IRF2 IRF4 IRS2 JAK1 JAK2 JAK3 A Phase III, Open-Label, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab TARGETS JUN KDM5A KDM5C KDM6A KDR KEAP1 KEL KIT KLHL6 (Anti-PD-L1 Antibody) Compared With Best Supportive Care Following Adjuvant Cisplatin-Based PD-L1 KMT2A (MLL) KMT2D (MLL2) KRAS LTK LYN MAF MAP2K1 (MEK1) MAP2K2 (MEK2) MAP2K4 Chemotherapy in Patients With Completely Resected Stage IB-IIIA Non-Small Cell Lung Cancer MAP3K1 MAP3K13 MAPK1 MCL1 MDM2 MDM4 MED12 MEF2B MEN1 MERTK MET MITF MKNK1 MLH1 MPL MRE11A MSH2 MSH3 LOCATIONS: Pennsylvania, Kansas, South Carolina, New York, Tennessee, New Mexico MSH6 MST1R MTAP MTOR MUTYH MYC MYCL (MYCL1) MYCN MYD88 NBN NF1 NF2 NFE2L2 NFKBIA NKX2-1 NOTCH1 NOTCH2 NOTCH3 NCT02657434 PHASE 3 NPM1 NRAS NT5C2 NTRK1 NTRK2 NTRK3 P2RY8 PALB2 PARK2 A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-Pd-L1 Antibody) in TARGETS PARP1 PARP2 PARP3 PAX5 PBRM1 PDCD1 (PD1) PDCD1LG2 (PD-L2) PDGFRA PDGFRB Combination With Carboplatin or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + PD-L1 PDK1 PIK3C2B PIK3C2G PIK3CA PIK3CB PIK3R1 PIM1 PMS2 POLD1 Pemetrexed in Patients Who Are Chemotherapy-Naive and Have Stage IV Non-Squamous Non-Small POLE PPARG PPP2R1A PPP2R2A PRDM1 PRKAR1A PRKCI PTCH1 PTEN Cell Lung Cancer PTPN11 PTPRO QKI RAC1 RAD21 RAD51 RAD51B RAD51C RAD51D RAD52 RAD54L RAF1 RARA RB1 RBM10 REL RET RICTOR LOCATIONS: California, Connecticut, Florida, Georgia, Illinois, Indiana, Kentucky, Michigan, Minnesota RNF43 ROS1 RPTOR SDHA SDHB SDHC SDHD SETD2 SF3B1 SGK1 SMAD2 SMAD4 SMARCA4 SMARCB1 SMO SNCAIP SOCS1 SOX2 NCT02713867 PHASE 3 SOX9 SPEN SPOP SRC STAG2 STAT3 STK11 SUFU SYK A Dose Frequency Optimization, Phase IIIB/IV Trial of Nivolumab 240 mg Every 2 Weeks vs TARGETS TBX3 TEK TET2 TGFBR2 TIPARP TNFAIP3 TNFRSF14 TP53 TSC1 Nivolumab 480 mg Every 4 Weeks in Subjects With Advanced or Metastatic Non-small Cell Lung PD-1 TSC2 TYRO3 U2AF1 VEGFA VHL WHSC1 WHSC1L1 WT1 XPO1 Cancer Who Received up to 12 Months of Nivolumab at 3 mg/kg or 240 mg Every 2 Weeks XRCC2 ZNF217 ZNF703

LOCATIONS: New Jersey, North Carolina, Pennsylvania, Kansas, New York, Tennessee, New Mexico

DNA GENE LIST: FOR THE DETECTION OF SELECT REARRANGEMENTS NCT01473095 PHASE 3 ALK BCL2 BCR BRAF BRCA1 BRCA2 CD74 KIT EGFR An Open-Label, Randomized Phase 3 Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab TARGETS ETV4 ETV5 ETV6 EWSR1 EZR FGFR1 FGFR2 FGFR3 KMT2A (MLL) Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Subjects With CTLA-4, PD-1 MSH2 MYB MYC NOTCH2 NTRK1 NTRK2 NUTM1 PDGFRA RAF1 Chemotherapy- Naïve Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC) RARA RET ROS1 RSPO2 SDC4 SLC34A2 TERC* TERT** TMPRSS2 *TERC is a ncRNA LOCATIONS: North Carolina, Pennsylvania, Kansas, South Carolina, New York **The promoter region of TERT interrogated

ADDITIONAL ASSAYS: FOR THE DETECTION OF SELECT CANCER BIOMARKERS Microsatellite status (MS) Tumor Mutational Burden (TMB)

Electronically Signed by Sample Preparation: Nonnenwald 2, 82377 Penzberg, Germany Electronically Signed by Jane Doctor, M.D., Ph.D. • Elizabeth Doctor, M.D., Medical Director • 15 January 2018 Sample Preparation: Nonnenwald 2, 82377 Penzberg, Germany Electronically Signed by Jane Doctor, M.D., Ph.D. • Elizabeth Doctor, M.D., Medical Director • 15 January 2018 Sample Preparation: Nonnenwald 2, 82377 Penzberg, Germany Foundation Medicine, Inc. • +49 7624 14 2098 Sample Analysis: Nonnenwald 2, 82377 Penzberg, Germany Foundation Medicine, Inc. • +49 7624 14 2098 Sample Analysis: Nonnenwald 2, 82377 Penzberg, Germany Foundation Medicine, Inc. • +49 7624 14 2098 Sample Analysis: Nonnenwald 2, 82377 Penzberg, Germany PAGE 12 of 19 APPENDIX — PAGE 18 of 22 APPENDIX — PAGE 19 of 22

Beschreibt laufende klinische Studien, Beinhaltet Varianten unbekannter Teilt Ihnen mit, was getestet wurde, für die Ihre Patienten infrage kommen Signifikanz (VUS) für den Fall, um Ihnen so ein umfassendes Bild könnten, inklusive NCT-Nummer, dass diese zukünftig klinisch von unseres Services zu geben. Phase, Studienname und Ort. Bedeutung sein werden.

FoundationOne®CDx Report: Unterstützt Sie bei Ihrer klinischen Entscheidungsfindung HABEN SIE FRAGEN ZUM ANFORDERUNGSPROZESS VON FOUNDATIONONE CDx? Kontaktieren Sie die Teilgemeinschaftspraxis Molekularpathlogie Südbayern telefonisch unter +49 89 2620817 21 oder per Fax unter +49 89 2620817 22 oder per Email an: [email protected] Adresse: TGMP, Nonnenwald 2, Gebäude 433 in 82377 Penzberg

1. FoundationOne®CDx Beispielbericht, 2018. Verfügbar unter www.foundationmedicine.de Disclaimer: Therapieentscheidungen liegen in der ärztlichen Verantwortung. Die im Report erwähnten Arzneistoffe sind möglicherweise für bestimmte Patienten nicht geeignet. Die Auswahl eines, aller oder keiner der Arzneistoffe liegt vollständig im Ermessen und der Verantwortung des behandelnden Arztes. Roche und Foundation Medicine® übernehmen keine Haftung für die Vollständigkeit der im Report zu findenden Informationen. Ein klinischer Nutzen wird nicht garantiert: Roche und Foundation Medicine® machen keine Versprechungen und geben auch keine Garantie dafür, dass ein bestimmter Arzneistoff für die Behandlung der Erkrankung bei einem Patienten wirksam sein wird bzw. dass eine Substanz mit fehlendem potentiellen klinischen Nutzen auch tatsächlich keinen klinischen Nutzen hat. Eine Erstattung wird nicht garantiert. Roche und Foundation Medicine® machen keine Versprechungen und geben auch keine Garantie, dass sie selbst oder eine dritte Partei, gleichgültig ob privat oder staatlich, einem Patienten die Kosten für FoundationOne®CDx erstatten werden. Der FoundationOne® CDx-Assay des Herstellers Foundation Medicine, Inc., 150 Second Street, 1st Floor, Cambridge, MA 02141, USA ist nach IVD-Richtlinie 98/79 EG der Europäischen Union zertifiziert und durch Foundation Medicines autorisiertem EU-Vertreter, Qarad b.v.b.a, Cipalstraat 3, 2440 Geel, Belgien für die CE-Kennzeichnung registriert. © 2018 Roche Pharma AG, Emil-Barell-Str. 1, 79639 Grenzach-Wyhlen; Telefon: +49 7624 14 2098; Fax: +49 7624 14 3846; E-Mail: germany.foundationmedicine@roche. com Roche ist der lizenzierte Anbieter von Foundation Medicine®-Produkten außerhalb der Vereinigten Staaten von Amerika. © 2018 Foundation Medicine, Inc. Foundation Medicine® und FoundationOne® CDx sind eingetragene Warenzeichen ONE-V-001-20140925 PR/FMI/1809/0032 | Datum der Erstellung: November 2018