1083P - KEYMAKER 02B: A randomized trial of pembrolizumab (pembro) alone or with investigational agents as first-line treatment for advanced melanoma

Background

Substudy 02B of the phase 1/2 KEYMAKER umbrella trial (NCT04305054) is evaluating first-line pembro (anti–PD-1) alone or with investigational agents for advanced melanoma. We present results from patients (pts) treated with pembro + vibostolimab (vibo; anti-TIGIT; arm 1), pembro alone (arm 2), quavonlimab (qmab; anti–CTLA-4) coformulated with pembro (qmab/pembro; arm 3), and qmab/pembro + lenvatinib (len; multitargeted TKI; arm 4).

Methods

Pts were aged ≥18 y with previously untreated unresectable stage III or IV cutaneous melanoma who had measurable disease per RECIST v1.1 and an ECOG PS of 0 or 1, but no active brain metastases. Pts were randomly assigned to open arms: pembro 200 mg IV Q3W + vibo 200 mg IV Q3W for ≤35 cycles (arm 1), pembro 400 mg IV Q6W for ≤18 cycles (arm 2), qmab 25 mg/pembro 400 mg IV Q6W for ≤18 cycles (arm 3), or qmab 25 mg/pembro 400 mg IV Q6W for ≤18 cycles + len 20 mg PO QD (arm 4). Primary end points were safety and ORR. DOR was secondary and PFS was exploratory.

Results

Overall, 232 pts were assigned to arm 1 (n = 90), arm 2 (n = 24), arm 3 (n = 31), or arm 4 (n = 87). Median (range) follow-up was 20.3 mo (10.7-42.4) for arm 1, 35.5 mo (18.3-43.1) for arm 2, 27.2 mo (18.2-33.6) for arm 3, and 14.9 mo (7.1-35.9) for arm 4. Efficacy data are reported in the table. Treatment-related AEs (TRAEs) occurred in 88% of pts in arm 1, 79% in arm 2, 97% in arm 3, and 97% in arm 4. Grade 3-5 TRAEs occurred in 31%, 29%, 42%, and 63% of pts, respectively. Three pts (3%) in arm 1 died due to immune-mediated AEs (myasthenic syndrome, myositis, and encephalitis).

Conclusions

Preliminary results from KEYMAKER-U02B showed promising antitumor activity for first-line pembro + vibo and qmab/pembro. Safety was generally manageable. Additional treatment arms will be reported when available. Adjuvant vibo/pembro is being explored in high-risk stage IIB-IV melanoma in the KEYVIBE-010 study. Table: 1083P

‘+’ indicates no PD by time of last disease assessment. NA, not applicable; NR, not reached.

aPFS data are not yet mature.

Clinical trial identification

NCT04305054; March 12, 2020.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Jemimah Walker, PhD, and Robert Steger, PhD, of ApotheCom (Yardley, PA, USA).

Legal entity responsible for the study

Merck Sharp & Dohme LLC, Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, NJ, USA.

Disclosure

R. Dummer: Financial Interests, Personal, Other, Consulting and/or advisory role: Novartis, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, MaviVAX SA, T3 Pharma, Pfizer, Simcere. R. Shapira: Financial Interests, Personal and Institutional, Invited Speaker: MSD, BMS, AstraZeneca; Financial Interests, Personal and Institutional, Advisory Board: MSD; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal and Institutional, Principal Investigator: MSD, BMS, AstraZeneca; Financial Interests, Personal, Invited Speaker: Novartis, GSK. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, Novartis, Merck Serono, Sun Pharma, Sanofi, Sandoz, Immunocore, Boehringer Ingelheim Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant, Advisory Role and Travel support: MSD, Pierre Fabre; Financial Interests, Personal, Other, Consultant and Advisory Role.Travel support: Pfizer/Array; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Consultant Role: Pfizer, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna; Financial Interests, Personal, Other, Consultant role and travel support: Bio-AI Health; Financial Interests, Personal, Advisory Board, Consultant and Advisory role: ValoTx; Financial Interests, Personal, Advisory Board, Consultant and Advisor role.Travel support: Replimmune; Financial Interests, Personal, Advisory Board, Advisor role: Bayer; Financial Interests, Personal, Other, Consultant and Advisory: Erasca; Financial Interests, Personal, Other, Consultant: Philogen; Financial Interests, Personal, Advisory Board: BionTech, Anaveon; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Member of Board of Directors, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR. C. Gaudy Marqueste: Financial Interests, Personal, Advisory Board: BMS, Pierre Fabre, MSD; Financial Interests, Personal, Invited Speaker: BMS, Pierre Fabre; Financial Interests, Institutional, Local PI: BMS, MSD, Pfizer, Amgen, GSK, Roche, Novartis, Pierre Fabre, Replimune, Jansen, Kartos, IFX, Huyabio, Regeneron, IO Biotech, Philogen, Sotio, Kinnate, AstraZeneca, Day One biopharmaceuticals, Sairopa, Catalyst, Sanofi, Immunocore; Other, Other, Travel expenses: BMS, Pierre Fabre, MSD. D. Portnoy: Non-Financial Interests, Personal and Institutional, Principal Investigator: Merck. M. Del Vecchio: Financial Interests, Personal, Advisory Board, Advisor and Consultant and Invited Speaker: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Immunocore; Non-Financial Interests, Principal Investigator, Clinical Trials: Bristol Myers Squibb, Merck Sharp & Dohme, Immunocore. G. Bar-Sela: Financial Interests, Personal, Invited Speaker: MSD, BMS, Novartis, Dexel, Medison, Abbot. J.E. Cohen: Financial Interests, Personal, Invited Speaker: Roche, Medison Pharma, Merck, AstraZeneca, Bristol Myers Squibb. A.M. Di Giacomo: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Pierre Fabre, Novartis, Immunocore; Financial Interests, Personal, Invited Speaker: Sanofi. A. Ribas: Financial Interests, Personal, Advisory Board, Honoraria for consulting: Amgen, Astra-Zeneca, Merck; Financial Interests, Personal, Advisory Board, Member of the Scientific Advisory Board: Apricity, Appia, Arcus, Compugen, Immpact, Lutris, MapKure, Merus, Synthekine, Tango; Financial Interests, Personal, Member of Board of Directors, Member of the Board of Directors: Arcus, Lutris; Financial Interests, Personal, Stocks/Shares, Stock ownership: 4C Biomed, Apricity, Appia, Arcus, Compugen, Highlight, ImaginAb, Immpact, Immunesensor, Inspirna, Isoplexis, Lutris, MapKure, Merus, Pluto, Synthekine, PACT Pharma, Tango, Advaxis, CytomX, RAPT, Kite-Gilead; Financial Interests, Personal, Advisory Board: Arsenal Bio; Financial Interests, Institutional, Funding: Agilent, Bristol Myers Squibb; Non-Financial Interests, Advisory Role, Member of the scientific advisory board: Highlight, Immunesensor, Inspirna, Pluto. C. Dutriaux: Financial Interests, Personal and Institutional, Advisory Board: BMS, MSD, Novartis, Pierre Fabre, Sanofi; Financial Interests, Personal and Institutional, Principal Investigator: BMS, MSD, Novartis, Pierre Fabre, Sanofi; Financial Interests, Personal and Institutional, Advisory Role: BMS, MSD, Novartis, Pierre Fabre, Sanofi. N. Jing, R. Lal: Financial Interests, Institutional, Full or part-time Employment: Merck & Co, Inc. C. Krepler: Financial Interests, Personal, Full or part-time Employment: Merck& Co; Financial Interests, Personal, Stocks/Shares: Merck& Co. G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, AstraZeneca UK Limited, Bayer Healthcare Pharmaceuticals, BioNTech SE, Boehringer Ingelheim Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG, Highlight Therapeutics S.L, IOBiotech, Immunocore Ireland Limited, Innovent Bioilogics USA Inc, Merck Sharp & Dohme, Novartis Pharma AG, PHMR Limited, Pierre Fabre, Regeneron Pharmaceuticals Inc, Scancell Limited, SkylineDX B.V; Non-Financial Interests, Principal Investigator, GL is PI on over 30 clinical trials: GL is PI on over 30 clinical trials. All other authors have declared no conflicts of interest.