Abstract 1082O
Background
Substudy 02C of the phase 1/2 KEYMAKER-U02 trial (NCT04303169) is evaluating neoadjuvant pembro with or without investigational agents followed by adjuvant pembro for stage IIIB-D melanoma. We present initial results from arm 4 (pembro + MK-4830 [anti-ILT4]) and arm 5 (favezelimab [anti-LAG-3] coformulated with pembro [fave/pembro]) and updated results from arm 1 (pembro + vibostolimab [vibo; anti-TIGIT]), arm 2 (pembro + gebasaxturev [geba; coxsackievirus A21]), and arm 3 (pembro alone).
Methods
Adults with resectable stage IIIB-D melanoma were randomly assigned to open arms. Patients (pts) received 2 doses of pembro 200 mg Q3W + vibo 200 mg Q3W in arm 1, 1 dose of pembro 400 mg + 5 doses of geba 3 × 108 TCID50 in arm 2, 1 dose of pembro 400 mg in arm 3, 2 doses of pembro 200 mg + MK-4830 800 mg Q3W in arm 4, and 2 doses of fave 800 mg/pembro 200 mg Q3W in arm 5. Resection occurred at week 6. At week 12, pts began adjuvant pembro 400 mg Q6W for ≤8 cycles. Primary end points were safety and pathologic complete response (pCR). Secondary end points included near pCR, partial pathologic response (pPR), and RFS. EFS was exploratory.
Results
117 pts were assigned to arm 1 (n = 26), arm 2 (n = 25), arm 3 (n = 15), arm 4 (n = 25), and arm 5 (n = 26). Median (range) follow-up was 29.9 (25.9-42.5) mo in arm 1, 29.7 (24.5-40.1) mo in arm 2, 34.3 (29.6-41.5) mo in arm 3, 15.2 (9.6-18.5) mo in arm 4, and 9.4 (4.1-12.6) mo in arm 5. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 8% of pts in arm 1, 28% in arm 2, 7% in arm 3, 16% in arm 4, and 15% in arm 5. No grade 5 TRAEs occurred. Efficacy is reported in the table. Median RFS and EFS were not reached in any arm. Table: 1082O
| Arm 1 pembro + vibo n = 26 | Arm 2 pembro + geba n = 25 | Arm 3 pembro alone n = 15 | Arm 4 pembro + MK-4830 n = 25 | Arm 5 fave/pembro n = 26 | |
| Major pathologic response (pCR + near pCR), % (95% CI) | 50 (30-70) | 40 (21-61) | 47 (21-73) | 32 (15-54) | 58 (37-77) |
| pCR, % (95% CI) | 38 (20-59) | 28 (12-49) | 40 (16-68) | 28 (12-49) | 38 (20-59) |
| Near pCR, % (95% CI) | 12 (2-30) | 12 (3-31) | 7 (ConclusionsAll arms had manageable safety in stage IIIB-D melanoma. With the promising antitumor activity observed in this study, further investigation of pembro + vibo and fave/pembro in this setting is warranted. RFS by major pathologic response will be presented. Clinical trial identificationNCT04303169, 6-26-2020. Editorial acknowledgementMedical 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 studyMerck Sharp & Dohme LLC, Rahway, NJ, USA. FundingMerck Sharp & Dohme LLC, Rahway, NJ, USA. DisclosureG.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. C. Robert: Financial Interests, Personal, Advisory Board, Consultancy fees: BMS, Roche, Pierre Fabre, Novartis, Sanofi, Msd, Pfizer, Sun Pharma, Merck, Ultimovacs, Regeneron, EGLE, Philogen, MAAT PHARMA; Financial Interests, Personal, Other, Steering Committee: Novartis, Regeneron, Pfizer, IO Biotech; Financial Interests, Personal, Other, IDMC: ULTIMOVACS; Financial Interests, Personal, Invited Speaker: Pierre Fabre, Sanofi, BMS, MSD, Novartis. 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, Astra Zenecca, Day One biopharmaceuticals, Sairopa, Catalyst, Sanofi, Immunocore; Other, Other, Travel expenses: BMS, Pierre Fabre, MSD. D. Portnoy: Financial Interests, Personal and Institutional, Principal Investigator: Merck & Co, Inc. R. Shapira: Financial Interests, Personal and Institutional, Advisory Board: MSD; Financial Interests, Personal and Institutional, Invited Speaker: MSD, BMS; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal and Institutional, Principal Investigator: MSD, BMS. J.E. Cohen: Financial Interests, Personal, Invited Speaker: Roche, Madison Pharma, Merck, AstraZeneca, Bristol Myers Squibb. M.A. Khattak: Financial Interests, Personal, Advisory Board: Moderna; Financial Interests, Personal, Invited Speaker: MSD. C. Lebbe: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Novartis, Amgen, Roche, Merck Serono, Sanofi, Pierre Fabre, Inflax; Financial Interests, Personal, Funding: Roche, Bristol Myers Squibb; Non-Financial Interests, Advisory Role: Bristol Myers Squibb, MSD, Novartis, Amgen, Roche, Merck Serono, Sanofi, Pierre Fabre; Other, Other, Honoraria, Speaker's Bureau, Research funding: Roche; Other, Other, Honoraira, Speaker's bureau, Travel, Accomodations, Expenses, Research funding, Board: Bristol myers Squibb; Other, Other, Honoraria, Speaker's bureau, Travel, Accommodations, Expenses, Board: Novartis, MSD; Other, Other, Honoraria, Speaker's bureau: Amgen; Other, Other, Honoraria, Travel, Accommodations, Expenses, Board: Pierre Fabre; Other, Other, Honoraria: Pfizer; Other, Other, Honoraria: Incyte; Other, Other, Travel, accommodations, Expenses, Board: Sanofi; Other, Other, Board: Avantis Medical Systems, Jazz Pharmaceuticals; Other, Other, Participation on a Data Safety Monitoring Board or Advisory Board: InflaRx. A.M. Menzies: Financial Interests, Personal, Advisory Board, advisory board: BMS, MSD, Novartis, Roche, Pierre Fabre, QBiotics. G. Markel: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Speaker’s Bureau: MSD. G. Bar-Sela: Financial Interests, Personal, Invited Speaker: MSD, BMS, Novartis, Dexel, Medison, Abbot. W.H. Sharfman: Financial Interests, Personal and Institutional, Research Grant: Merck, BMS; Financial Interests, Personal and Institutional, Advisory Role: Merck, BMS; Financial Interests, Institutional, Research Grant: AZ, Novartis, Genentech. C. Pages: Non-Financial Interests, Personal, Advisory Board: NSD. O. Hamid: Financial Interests, Personal, Advisory Board: Alkermes, Amgen, Bactonix, Beigene, Eisai, GigaGen, GritBio, Instilbio, IO Biotech, Janssen, KSQ, Obsidian, Tempus, Vial; Financial Interests, Personal, Stocks/Shares: Bactonix; Financial Interests, Personal and Institutional, Advisory Board: BioAtla, BMS, Roche Genentech; Financial Interests, Personal and Institutional, Principal Investigator: BioAtla, BMS; Financial Interests, Personal and Institutional, Other, Contracted Research for Institution: BioAtla, Roche Genentech; Financial Interests, Personal and Institutional, Speaker’s Bureau: BMS; Financial Interests, Personal and Institutional, Advisory Board, Contracted Research for Institution: BMS, Georgiamune, GSK, Idera, Immunocore, Incyte, Iovance, Merck, Moderna, Novartis, Pfizer, Regeneron, Zelluna; Financial Interests, Personal and Institutional, Principal Investigator, Contracted Research for Institution: Georgiamune, GSK, Immunocore, Incyte, Iovance, Merck; Financial Interests, Personal and Institutional, Speaker’s Bureau, Contracted Research for Institution: Immunocore, Novartis, Pfizer, Regeneron; Financial Interests, Institutional, Other, Contracted Research for Institution: Arcus, Akeso, Aduro, Cytomx, Exelixis, Merck Serono, Next Cure, Torque. J.M. Mehnert: Financial Interests, Institutional, Advisory Board: Regeneron, Merck. N. Jing, C. Krepler: Financial Interests, Institutional, Full or part-time Employment: Merck & Co, Inc. M. Kalabis: Financial Interests, Personal, Full or part-time Employment: Merck & Co, Inc; Financial Interests, Personal, Stocks/Shares: Merck & Co, Inc. R. Dummer: Financial Interests, Personal, Advisory Board: Novartis, Merck Sharp & Dhome (MSD), Bristol Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, T3 Pharma, MaxiVAX SA, Pfizer, Simcere. All other authors have declared no conflicts of interest. 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