Abstract 718TiP
Background
The phase II KEYNOTE-057 study showed that pembro monotherapy provided effective antitumor activity and acceptable safety in BCG-unresponsive HR NMIBC pts. Combining pembro and BCG earlier in the disease course might provide anticancer activity superior to that of BCG monotherapy. KEYNOTE-676 (NCT03711032) is an open-label, comparator-controlled, phase III study of pembro + BCG vs BCG monotherapy in pts with HR NMIBC. The initial study (cohort A) is enrolling pts with persistent/recurrent HR NMIBC after BCG induction. Cohort B is a new, randomized cohort that will be used to evaluate BCG treatment–naive or treatment-remote (> 2 years prior) pts.
Trial design
Approximately 975 pts with blinded independent central review–confirmed histologic diagnosis of HR NMIBC (T1, high-grade Ta or carcinoma in situ [CIS]) will be included in cohort B. Pts must have undergone cystoscopy/TURBT ≤12 wk before random allocation, have provided tissue for biomarker analysis, and have an ECOG PS 0-2. Pts must not have been treated with BCG ≤2 y before randomization. Pts will be randomly assigned 1:1:1 to receive pembro 400 mg IV Q6W + BCG reduced maintenance (BCG induction then 1 maintenance cycle); pembro 400 mg IV Q6W + BCG full maintenance (BCG induction then maintenance cycles up to 18 mo); or BCG monotherapy (BCG induction then BCG maintenance up to 18 mo). Randomization will be stratified by NMIBC stage (CIS ± papillary disease or papillary disease alone) and PD-L1 expression (combined positive score [CPS] ≥10 or CPS <10). Disease status will be assessed by use of cystoscopy, urine cytology, and biopsy (as appropriate per protocol) Q12W from randomization through year 2, then Q24W through year 5; imaging with CTU will occur Q72W. The primary end point is event-free survival (EFS) in all pts. Secondary end points are complete response rate, duration of response (DOR), and 12-mo DOR rate for pts with CIS and recurrence-free survival, overall survival, disease-specific survival, time to cystectomy, 24-mo EFS rate, time to deterioration in health-related quality of life, safety, and tolerability.
Clinical trial identification
NCT03711032, October 18, 2018.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, 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
S.F. Shariat: Financial Interests, Personal, Other, Honoraria: Astellas, AstraZeneca, Bayer, BMS, Cepheid, Ferring, Ipsen, Janssen, Lilly, Olympus, Pfizer, Pierre Fabre, Richard Wolf, Roche, Sandochemia, Sanofi, Takeda, Urogen; Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Astellas, AstraZeneca, Bayer, BMS, Cepheid, Ferring, Ipsen, Janssen, Lilly, Olympus, Pfizer, Pierre Fabre, Richard Wolf, Roche, Sandochemia, Sanofi, Takeda, Urogen; Financial Interests, Personal, Speaker’s Bureau: Astellas, AstraZeneca, Bayer, BMS, Cepheid, Ferring, Ipsen, Janssen, Lilly, Olympus, Pfizer, Pierre Fabre, Richard Wolf, Roche, Sandochemia, Sanofi, Takeda, Urogen, Movember Foundation; Financial Interests, Personal, Other: Patents. G. Steinberg: Financial Interests, Personal, Other, Honoraria: Merck, Pfizer, Janssen, Photocure, Urogen, BMS, CG Oncology, Engene Bio, AstraZeneca, Fergene, Regeneron, Verity Pharm, Fidia Farmaceuticals, Seagen; Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Merck, Pfizer, Janssen, Photocure, Urogen, BMS, CG Oncology, Engene Bio, AstraZeneca, Fergene, Regeneron, Verity Pharm, Fidia Farmaceuticals, Seagen; Financial Interests, Personal, Leadership Role: Epivax Therapeutics; Financial Interests, Personal, Stocks/Shares: Urogen, Epivax Therapeutics. A.M. Kamat: Financial Interests, Personal, Advisory Role, Advisory/consultancy: Abbott Molecular, Arquer, ArTara, Asieris, AstraZeneca, BioClin Therapeutics, Biological Dynamics, BMS, Cepheid, Cold Genesys, Eisai, Engene, Inc., Ferring, FerGene, Imagin, Incyte DSMBJanssen, MDxHealth, Medac, Merck, Pfizer, Photocure, ProTara,Roviant,; Financial Interests, Personal, Research Grant: Adolor, BMS, FKD Industries, Heat Biologics, Merck, Photocure, SWOG/NIH, SPORE, AIBCCR. N.D. Shore: Financial Interests, Personal, Advisory Role, Advisory/consultancy: AbbVie, Amgen, Astellas, AstraZeneca, Aurora Oncology, Bayer, BMS, Boston Scientific, Clovis Oncology, Cold Genesys, Dendreon, Exact Imaging, Exact Sciences, FerGene, Foundation Medicine, GenesisCare, Invitae, Janssen, MDxhealth, Merck, Myovant, Myriad,; Financial Interests, Personal, Speaker’s Bureau: Astellas, AstraZeneca, Bayer, Clovis Oncology, Foundation Medicine, Guardant, Janssen, Merck, Myovant, Pfizer, Tolmar. S. Alanee: Financial Interests, Personal, Advisory Role: Merck, AstraZeneca, IncellDX; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Funding: Merck; Financial Interests, Personal, Member of the Board of Directors: IncellDX; Financial Interests, Personal, Stocks/Shares: IncellDX. H. Nishiyama: Financial Interests, Personal, Advisory Role: MSD, Lilly, Bayer, Yakuhin, Janssen, Chugai Pharma; Financial Interests, Personal, Speaker’s Bureau: MSD,Chugai Pharmaceutical, Olympus; Financial Interests, Institutional, Research Grant: Astellas, Ono Pharmaceutical, Takeda Pharmaceutical, Bayer. K. Nam: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. J.L. Godwin: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. E. Kapadia: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. N. Hahn: Financial Interests, Personal, Advisory Role: Merck, Genentech, GlaxoSmithKline, Ferring, Champions Oncology, Health Advances, Keyquest Health, Guidepoint Global, Seattle Genetics, Mirati, Incyte, TransMed, CicloMed, Janssen, Pfizer, Boehringer Ingelheim, Pfizer, EMD Serono; Financial Interests, Personal, Speaker’s Bureau: Creative Educational Concepts, Large Urology Group Practice Association; Financial Interests, Institutional, Research Grant: HTG Molecular Diagnostics, AstraZeneca, Bristol Myers-Squibb, Genentech, Seattle Genetics, OncoGenex, Pieris, Inovio, Principia Biopharm.