BACKGROUND METHODS

Avelumab (anti–PD-L1) in patients with platinum- • SCCHN is one of the most common cancers worldwide1 • Eligible patients were aged ≥18 years with R/M SCCHN of the oral cavity, – HPV status was assessed centrally in all patients using p16 IHC assay – R/M disease develops in approximately 65% of cases; median OS is <1 year1 oropharynx, hypopharynx, or larynx; had received ≥1 line of platinum • Patients received avelumab 10 mg/kg every 2 weeks until progression, • Systemic treatment options for R/M SCCHN include cetuximab (anti–epidermal therapy with disease progression or recurrence within 6 months of the last refractory/ineligible recurrent or metastatic squamous unacceptable toxicity, or withdrawal from trial occurred growth factor receptor monoclonal antibody) + platinum-based chemotherapy dose; measurable disease according to Response Evaluation Criteria in Solid 2 cell carcinoma of the head and neck (R/M SCCHN): or single-agent nonplatinum chemotherapy for platinum-ineligible patients Tumors version 1.1 (RECIST 1.1); and an Eastern Cooperative Oncology Group • A sample size of 150 patients was planned to provide 95% Clopper-Pearson CIs • Anti–PD-1 immune checkpoint inhibitors have proven to be effective treatment performance status (ECOG PS) score of 0 or 1 for an ORR of 10% (95% CI: 5.7%-16.0%) and 20% (95% CI: 13.9%-27.3%) in the case options as monotherapy in platinum-refractory patients, or as monotherapy or in of 15 and 30 responders, respectively results from a phase 1b cohort combination with chemotherapy in first-line R/M SCCHN2-5 • Patients were not selected based on PD-L1 or HPV status • Avelumab, an anti–PD-L1 immune checkpoint inhibitor, has shown clinical – PD-L1+ status was assessed centrally using immunohistochemistry (IHC); 73-10 • Key endpoints: best overall response and PFS (assessed by independent review activity including durable responses in patients with a range of tumor types6-8 pharmDx assay (PD-L1 expression in ≥1% of tumor cells) committee [IRC] and investigator per RECIST 1.1), OS, and safety

RESULTS

J. Guigay1, K-W. Lee2, M. Patel3, A. Daste4, D. J. Wong5, S. Goel6, M. Gordon7, M. Gutierrez8, • Between 24 April 2015 and 24 November 2015, 153 patients were enrolled and • Immune-related ORR by investigator per modified immune-related response Figure 3. (A) PFS by RECIST 1.1 per IRC and investigator and (B) OS 9 10 11 12 13 14 received avelumab criteria was 13.7% (95% CI: 8.7%-20.2%) A. Balmanoukian , C. Le Tourneau , A. Mita , D. Vansteene , U. Keilholz , P. Schöffski , 100 – Patients had received a median of 2 prior lines of therapy for metastatic or locally A 15 16 17 18 90 IRC Investigator advanced disease (Table 1), and 12 patients (7.8%) were platinum ineligible Figure 1. Time to and duration of response for patients with confirmed objective (N=153) (N=153) H. J. Grote , D. Zhou , M. Bajars , N. Penel 80 • At data cutoff (31 December 2017), median follow-up was 27.9 months response per (A) IRC and (B) investigator Events, n (%) 119 (77.8) 130 (85.0) 1Antoine Lacassagne Cancer Center, FHU OncoAge Université Côte d’Azur, Nice, France; 2Seoul National University Bundang Hospital, Seoul National 70 Median (95% CI), 3 4 (range, 25-32 months), and 10 patients (6.5%) remained on treatment A 60 1.4 (1.4-2.6) 1.8 (1.4-2.7) University College of Medicine, Republic of Korea; Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, Florida, USA; Groupe Hospitalier months Saint André, Hôpital Saint André, Bordeaux, France; 5UCLA Department of Medicine, Los Angeles, California, USA; 6Montefiore Medical Center PRIME, – Median duration of treatment was 3.0 months (range, 0.5-29.0 months) 50 New York, New York, USA; 7HonorHealth Research Institute, Scottsdale, Arizona, USA; 8Hackensack University Medical Center, Hackensack, New Jersey, PFS (%) 40 9 10 • Based on IRC and investigator assessment, respectively, median time to USA; The Angeles Clinic and Research Institute, Los Angeles, California, USA; Institut Curie, Centre de Lutte Contre le Cancer (CLCC) de Paris, Paris, 30 11 12 response was 2.8 months (range, 1.3-11.0 months) and 3.3 months (range, 1.2-5.5 France; Cedars-Sinai Medical Center, Los Angeles, California, USA; Institut de Cancérologie de l’Ouest, site René Gauducheau, Département d’Oncologie 20 13 14 months); median duration of response was not estimable (95% CI: 4.2 months-not Médicale, Saint Herblain, France; Charité Comprehensive Cancer Institute, Berlin, Germany; Department of General Medical Oncology, Leuven Cancer 10 15 estimable) and not estimable (95% CI: 8.3 months-not estimable; Figure 1) Institute, University Hospitals Leuven and Faculty of Medicine, Research Unit Laboratory of Experimental Oncology, KU Leuven, Leuven, Belgium; Merck 0 KGaA, Darmstadt, Germany; 16Merck Serono Pharmaceutical R&D Co., Beijing, China; an affiliate of Merck KGaA, Darmstadt, Germany;17 EMD Serono Patients 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 18 Months Research & Development Institute, Inc., Billerica, Massachusetts, USA; a business of Merck KGaA, Darmstadt, Germany; Lille University and Oscar Table 1. Key baseline characteristics No. at risk Lambret Cancer Center, Medical Oncology Department, Lille, France IRC 153 62 34 19 16 11 10 9 9 9 9 9 7 6 1 0 Characteristic N=153 Investigator 153 72 48 31 28 20 18 15 15 11 11 11 9 7 1 0 B 100 Median age (range), years 63 (37-91) N=153 90 Events, n (%) 129 (84.3) Sex, n (%) 80 Median (95% CI), months 8.0 (6.5-10.2) Male 125 (81.7) 0 5 10 15 20 25 30 35 40 70 SCOPE Months OS rate (95% CI), % Female 28 (18.3) 60 1-year 35.9 (28.3-43.6) ECOG PS, n (%) Complete reponse Partial response Progressive disease Ongoing response or stable disease End of treatment 50 2-year 17.1 (11.5-23.7) • We report the efficacy and safety data from a cohort of patients with R/M SCCHN OS (%) 0 40 (26.1) B 40 treated with avelumab monotherapy in the phase 1, open-label, multicenter JAVELIN 1 113 (73.9) 30 20 PD-L1 status, n (%) Solid Tumor trial 10 Positive 107 (69.9) 0 Negative 30 (19.6) 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 Not evaluable 16 (10.5) Months No. at risk 153 138 114 92 74 65 53 48 41 33 29 25 24 20 9 2 0

HPV status, n (%) Patients CONCLUSIONS Positive 39 (25.5) • In patients with PD-L1+ (n=107) or PD-L1− (n=30) tumors: Negative 99 (64.7) • Avelumab showed clinical activity and an acceptable safety profile in heavily Missing 15 (9.8) – Median PFS by RECIST 1.1 per IRC was 1.4 months (95% CI: 1.4-2.8 months) vs 1.4 months (95% CI: 1.3-2.7 months) pretreated patients with platinum-refractory/ineligible R/M SCCHN Site of primary tumor, n (%) Hypopharynx 20 (13.1) – Median PFS by RECIST 1.1 per investigator was 1.8 months (95% CI: 1.4-3.5 Larynx 18 (11.8) months) vs 1.5 months (95% CI: 1.3-4.0 months) • Treatment-related adverse events (TRAEs) were grades 1-2 in the majority of cases (73 of Oral cavity 53 (34.6) 0 5 10 15 20 25 30 35 40 – Median OS was 7.9 months (95% CI: 6.1-10.6 months) vs 8.9 months (95% CI: Oropharynx 34 (22.2) Months 6.7-15.0 months) 83 cases; 88%), and a low proportion of patients had grade ≥3 TRAEs (10 of 83; 12.0%) Other* 28 (18.3) • Median immune-related PFS by investigator per modified immune-related • Responses were irrespective of PD-L1 status Prior lines of anticancer therapy for metastatic or locally Figure 2. Confirmed best overall response by PD-L1 and HPV subgroups per response criteria was 2.8 months (95% CI: 2.7-4.1 months) advanced disease, n (%) (A) IRC and (B) investigator – 0 22 (14.4) Table 3. Safety overview Objective response rates (ORRs) were higher in patients with PD-L1+ tumors (n=107; 1 49 (32.0) A Subgroups N Patients ith an objective response n (%) 95% CI* 2 38 (24.8) Overall population 153 14 (9.2) 5.1-14.9 n (%) N=153 ORR by IRC, 10.3%; ORR by investigator, 15.0%) vs PD-L1− tumors (n=30; ORR by IRC, 3 28 (18.3) PD-L1 expression (≥1%) AE* 3.3%; ORR by investigator, 6.7%) and in patients with HPV+ tumors (n=39; ORR by IRC, ≥4 15 (9.8) Positive 107 11 (10.3) 5.2-17.7 Any grade 149 (97.4) Missing 1 (0.7) Negative 30 1 (3.3) 0.1-17.2 Grade ≥3 91 (59.5) 15.4%; ORR by investigator, 17.9%) vs HPV− tumors (n=99; ORR by IRC, 5.1%; ORR by Not evaluable 16 2 (12.5) 1.6-38.3 * Includes salivary glands (n=3), nasal cavity and sinuses (n=2), nasopharynx (n=2), and other (n=21) TRAE HPV status Any grade 83 (54.2) investigator, 11.1%) Positive 39 6 (15.4) 5.9-30.5 Table 2. Confirmed best overall response per IRC and investigator Negative 99 5 (5.1) 1.7-11.4 Grade ≥3 10 (6.5) Unknown 15 3 (20.0) 4.3-48.1 Serious TRAE 6 (3.9) – Progression-free survival (PFS) and overall survival (OS) were similar in both PD-L1+ and N=153 Characteristic 0 10 20 30 40 50 60 70 80 90 100 PD-L1− subgroups IRC Investigator TRAE leading to permanent discontinuation 4 (2.6) B Subgroups N Patients ith an objective response n (%) 95% CI* TRAE leading to death 0 Confirmed best overall response, n (%) Overall population 153 20 (13.1) 8.2-19.5 † Complete response 2 (1.3) 5 (3.3) Immune-related AE Partial response 12 (7.8) 15 (9.8) PD-L1 expression (≥1%) Any grade 23 (15.0) Positive 107 16 (15.0) 8.8-23.1 Grade ≥3 3 (2.0) GET POSTER PDF Stable disease 46 (30.1) 50 (32.7) Negative 30 2 (6.7) 0.8-22.1 Infusion-related reaction‡ GET PLAIN LANGUAGE SUMMARY Noncomplete response/nonprogressive disease 1 (0.7) 0 Not evaluable 16 2 (12.5) 1.6-38.3 Copies of this poster obtained through quick response (QR) code are for personal Any grade 23 (15.0) Progressive disease 67 (43.8) 66 (43.1) use only and may not be reproduced without permission from ESMO and the author Please scan this quick response (QR) code with your smartphone app to HPV status Grade ≥3 0 of this poster view a plain language summary of the accepted scientific abstract Nonevaluable* 25 (16.3) 17 (11.1) Positive 39 7 (17.9) 7.5-33.5 Correspondence: Joel Guigay, [email protected] Negative 99 11 (11.1) 5.7-19.0 AE, adverse event; TRAE, treatment-related AE Unknown 15 2 (13.3) 1.7-40.5 ORR (95% CI), %† 9.2 (5.1-14.9) 13.1 (8.2-19.5) * AEs were graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events version 4.0 † Based on a prespecified list of Medical Dictionary for Regulatory Activities (MedDRA) preferred terms followed by comprehensive medical review. 0 10 20 30 40 50 60 70 80 90 100 ‡ Composite term, which includes AEs categorized as infusion-related reaction, drug hypersensitivity, or hypersensitivity reaction that occurred on the * Includes missing and not assessable day of infusion or day after infusion, in addition to signs and symptoms of infusion-related reaction that occurred on the same day of infusion and † *95% exact CIs calculated using the Clopper-Pearson method Defined as the proportion of patients with a complete or partial response resolved within 2 days (including AEs classified by investigators as related or unrelated to treatment)

REFERENCES 1. Chow LQM. N Engl J Med. 2020;382(1):60-72. 2. NCCN Clinical Practice Guidelines in Oncology. Head and neck cancers. V1.2020. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf. Accessed August 3, 2020. 3. Burtness B, et al. Lancet. 2019;394(10212):1915-28. 4. Ferris RL, et al. Oral Oncol. 2018;81:45-51. 5. Ferris RL, et al. Ann Oncol. 2020;31(7):942-50. 6. Gulley JL, et al. Lancet. 2017;18(5):599-610. 7. Keilholz U, et al. J Immunother Cancer. 2019;7(1):12. 8. Hassan R, et al. JAMA Oncol. 2019;5(3):351-7. DISCLOSURES Joel Guigay reports providing a consulting or advisory role for AstraZeneca, Bristol Myers Squibb, EMD Serono (a business of Merck KGaA, Darmstadt, Germany), and Innate Pharma; and has received research funding from Bristol Myers Squibb, EMD Serono, and Merck & Co. Keun-Wook Lee has received honoraria from Bristol Myers Squibb, Eli Lilly, and Genexine; and research funding from AbbVie, ALX Oncology, Array BioPharma, ASLAN Pharmaceuticals, AstraZeneca/MedImmune, BeiGene, Five Prime Therapeutics, Genexine, Green Cross Corporation, LSK BioPartners, MacroGenics, Merck KGaA, Merck & Co., Ono Pharmaceutical, Pharmacyclics, Pfizer, and Zymeworks.Manish Patel has received honoraria from AbbVie, Bayer, Genentech, Janssen Pharmaceutica, Pharmacyclics, and Pfizer; provided speakers services for Celgene, EMD Serono, and Exelixis; and has received research funding from Acerta Pharma, ADC Therapeutics, Agenus, Aileron Therapeutics, AstraZeneca, Bicycle Therapeutics, BioNTech, Boehringer Ingelheim, Calithera Biosciences, Celgene, Checkpoint Therapeutics, Ciclomed, Covis Pharma, Curis, Cyteir Therapeutics, Daiichi Sankyo, eFFECTOR Therapeutics, Eli Lilly, EMD Serono, Evelo Biosciences, Forma Therapeutics, Genentech/Roche, Gilead, GlaxoSmithKline, H3 Biomedicine, Hengrui Therapeutics, Hutchinson MediPharma, Ignyta, Incyte, Jacobio Pharmaceuticals, Janssen Pharmaceutica, Jounce Therapeutics, KLUS Pharma, Kymab, Loxo Oncology, LSK BioBartners, Lycera, MacroGenics, Merck KGaA, Millennium Pharmaceuticals, Mirati Therapeutics, Moderna, Pfizer, Phoenix Molecular Designs, Placon Therapeutics, Portola Pharmaceuticals, Prelude Therapeutics, Qilu Puget Sound Biotherapeutics, Revolution Medicines, Ribon Therapeutics, Seven and Eight Biopharmaceuticals, Syndax, Synthorx, Stemline Therapeutics, Taiho Pharmaceutical, Takeda, Tesaro, TopAlliance, Vedanta Biosciences, Verastem Oncology, Vigeo Therapeutics, and Xencor.Amaury Daste reports providing a consulting or advisory role for and receiving reimbursement for travel and accommodation expenses from Bristol Myers Squibb and Merck KGaA. Deborah J. Wong reports providing a consulting or advisory role for Bristol Myers Squibb and Sanofi-Aventis; and has received research funding from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Enzychem Lifesciences, F-star, Genentech, Iovance Biotherapeutics, Kura Oncology, Merck KGaA, Pfizer, Regeneron, and Sanofi-Aventis.Michael Gordon reports providing a consulting or advisory role for Deciphera Pharmaceuticals, ImaginAb, Redhill Biopharma, and TRACON Pharmaceuticals; and owns stock in Caremission and Medelis. Martin Gutierrez reports providing a consulting or advisory role for Guardant360; speakers services for Merck KGaA; has received research funding from Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Care Progress, Celgene, Compass Therapeutics, Constellation Pharmaceuticals, CytRx, Eisai, Esanex, Genentech, Incyte, Infinity Pharmaceuticals, Janssen Pharmaceutica, Karyopharm Therapeutics, MedImmune, Merck KGaA, Mirati Therapeutics, Moderna, Pfizer, Regeneron, Sanofi, Seattle Genetics, Tesaro, and Vendata Biosciences; owns stock in Cota Healthcare; and is an employee of Reginal Cancer Care Associates.Ani Balmanoukian reports providing speakers services for AstraZeneca, Bristol Myers Squibb, Eli Lilly, Genentech, and Merck KGaA; and has received research funding from Arcus Biosciences, Bristol Myers Squibb, Genentech, GlaxoSmithKline, MedImmune, and Merck KGaA. Christophe Le Tourneau has received honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, EMD Serono, GlaxoSmithKline, Merck & Co., Nanobiotix, Rakuten, Roche, and Seattle Genetics; provided a consulting or advisory role for Idem Healthcare; has received reimbursement for travel and accommodation expenses from AstraZeneca, Bristol Myers Squibb, EMD Serono, and Merck & Co. Damien Vansteene reports providing a consulting or advisory role for Nestle and Nutricia. Patrick Schöffski has received honoraria from Deciphera Pharmaceuticals, Blueprint Medicines, and Boehringer Ingelheim; provided a consulting or advisory role for Adaptimmune, Blueprint Medicines, Deciphera, Eisai, Eli Lilly, Ellipses Pharma, Exelixis, Genmab, Intellisphere, Loxo Oncology, Merck KGaA, Plexxikon, Servier, and Transgene; research funding from CoBioRes, Eisai, G1 Therapeutics, Novartis, and PharmaMar; and reimbursement for travel and accommodation expenses from Ipsen and Merck & Co. Hans Juergen Grote is an employee of Merck KGaA, Darmstadt, Germany. Dongli Zhou is an employee of Merck Serono Pharmaceutical R&D Co., an affiliate of Merck KGaA, Darmstadt, Germany.Marcis Bajars is an employee of EMD Serono Research & Development Institute, Inc., a business of Merck KGaA, Darmstadt, Germany. All other authors have nothing to disclose. ACKNOWLEDGMENTS The authors would like to thank the patients and their families, investigators, co-investigators, and the study teams at each of the participating centers and at Merck KGaA, Darmstadt, Germany. This trial was sponsored by Merck KGaA, Darmstadt, Germany, as part of an alliance between Merck KGaA and Pfizer. Medical writing support was provided by Eleanor Green of ClinicalThinking and was funded by Merck KGaA and Pfizer. Abstract No. 4024. Presented at the ESMO Virtual Congress 2020, 19–21 September 2020.