Abstract 1092TiP
Background
Pembro is a SOC for unresectable or metastatic mel and adjuvant treatment (tx) of stage III mel. There is need to improve outcomes in patients (pts) with advanced mel and brain metastases (BM) and to reduce tumor burden before surgery.
Trial design
KEYMAKER-U02 is a phase I/II, rolling arm, multicenter, open-label, adaptive design study of Inv agents ± pembro or pembro alone in mel. Recruitment is ongoing in 4 substudies. Substudy 02A: Pts with unresectable stage III/IV PD-1–refractory mel (disease progression after ≥2 doses of anti–PD-1/PD-L1 therapy) will be randomized equally to tx arms with ≥1 Inv agent(s) ± pembro. Planned enrollment is ∼100 pts/arm. Substudy 02B: Pts with unresectable tx-naive stage III/IV mel will be randomized 2:1 to combination of ≥1 Inv agent(s) ± pembro or pembro alone stratified by baseline LDH status (normal/elevated) and prior adjuvant anti–PD-1 therapy (yes/no). Planned enrollment is ∼90 pts in the combination arms, ∼45 in the pembro arm. Substudy 02C: Pts with stage IIIB/IIIC/IIID mel who are eligible for neoadjuvant therapy will be randomized to combination of ≥1 Inv agent(s) ± pembro or pembro alone. Surgical resection will occur 6 weeks after the first dose of neoadjuvant tx. Planned enrollment is ∼25 pts in the combination arms, ∼15 in the pembro arm. Substudy 02D: Pts with stage IV mel who have ≥1 and ≤5 measurable BM by RECIST v1.1, confirmed by blinded independent central review (BICR), no neurologic symptoms of BM, and who have not received >3 lines of prior tx are eligible. Pts will be included in PD-1–naive or PD-1–exposed cohorts and randomized to combination arms of ≥1 Inv agent(s) with pembro. Planned enrollment is ∼50 pts (≤100 for PD-1–naive cohort) per each Inv agent arm. Tx will continue for ≤2 y in substudies 02A, 02B, and 02D, and ≤1 y in 02C. Primary end points are safety for all substudies; ORR by BICR per RECIST v1.1 for substudies 02A, 02B, and 02D; and pathological CR (pCR) by central review for substudy 02C. Secondary end points are DOR for substudies 02A and 02B; recurrence-free survival, near pCR, and pathological PR rate for substudy 02C; and DOR, PFS, BM response rate per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM), and BM-DOR per RANO-BM for substudy 02D.
Clinical trial identification
NCT, first posted NCT04305041 (substudy 02A), March 12, 2020 NCT04305054 (substudy 02B), March 12, 2020 NCT04303169 (substudy 02C), March 10, 2020 NCT04700072 (substudy 02d), January 7, 2021.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Jemimah Walker, PhD, and Doyel Mitra, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
R. Dummer: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Roche, Bristol-Myers Squibb, MSD, Novartis, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Alligator Bioscience, touchIME, MaxiVax, Regeneron; Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Bristol-Myers Squibb, MSD, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator Bioscience, MaxiVax, touchIME; Financial Interests, Institutional, Research Grant: Roche, Bristol-Myers Squibb, Novartis, MSD, Amgen. G.V. Long: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Aduro Biotech, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Hexal, Highlight Therapeutics, Merck Sharp & Dohme, Novartis, OncoSec, Pierre Fabre, QBiotics, Regeneron, Skyline Dx, Specialised Therapeutics, Array BioPharma. A.C. Pavlick: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Bristol-Myers Squibb, Merck, Regeneron; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb, Merck, Regeneron, Seattle Genetics. M.A. Postow: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Bristol-Myers Squibb, Novartis, Array BioPharma, Newlink Genetics, Incyte, Merck, Eisai, Pfizer; Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb, Merck; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb, Novartis, Array BioPharma, Infinity Pharmaceuticals, Rgenix, Merck, AstraZeneca/MedImmune. A. Ribas: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Merck, Amgen, Novartis, Chugai Pharma, Sanofi; Financial Interests, Personal, Leadership Role: PACT Pharma, Arcus Biosciences, Lutris; Financial Interests, Personal, Stocks/Shares: Compugen, CytomX Therapeutics, Five Prime Therapeutics, Advaxis, Arcus Biosciences, Tango Therapeutics, PACT Pharma, Merus, Rgenix, ImaginAb, Lutris, Highlight Therapeutics, MapKure, 4c Biomed, Kite/Gilead, RAPT Therapeutics, Isoplexis; Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme, Novartis, Amgen, Chugai/Roche, Sanofi, Vedanta Biosciences, AstraZeneca; Financial Interests, Institutional, Research Grant: Agilent, Bristol-Myers Squibb. C. Robert: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Bristol-Myers Squibb, Roche, Amgen, Novartis, Pierre Fabre, MSD, Sanofi, AstraZeneca, Pfizer. R.A. Scolyer: Financial Interests, Personal, Full or part-time Employment: Royal Prince Alfred Hospital; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, NeraCare GmbH, Novartis Australia, Amgen, Myriad Genetics, Novartis, QBiotics ; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Bristol-Myers Squibb, Novartis Australia; Financial Interests, Institutional, Research Grant: The Ainsworth Foundation; Financial Interests, Personal, Research Grant: National Health and Medical Research Council. J.M. Taube: Financial Interests, Personal, Stocks/Shares: Akoya Biosciences; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Akoya Biosciences, Bristol-Myers Squibb, Merck, AstraZeneca; Financial Interests, Personal, Research Grant: Akoya Biosciences, Bristol-Myers Squibb; Financial Interests, Personal, Royalties: Patent for image processing for multiplex IF/IHC. M. Tetzlaff: Financial Interests, Personal, Other, Honoraria: Myriad Pharmaceuticals, Merck, NanoString Technologies, Novartis; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Myriad Pharmaceuticals, Merck, NanoString Technologies, Novartis; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Myriad Pharmaceuticals, Nanostring Technologies. S. Su: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. R. Singh: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. S.J. Diede: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme. H.A. Tawbi: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Novartis, Bristol-Myers Squibb, Genentech/Roche, Merck, Array BioPharma, Eisai, Iovance Biotherapeutics; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb, Novartis, Merck, GlaxoSmithKline, Genentech/Roche, Celgene.