LBA7 - Nivolumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin alone for previously untreated unresectable or metastatic urothelial carcinoma: Results from the phase III CheckMate 901 trial

Background

Cisplatin (cis)-based chemotherapy (chemo) has been the first-line standard of care (SOC) for cis-eligible patients (pts) with unresectable/metastatic urothelial carcinoma (mUC) for decades, and prior attempts to improve upon this treatment have been unsuccessful. We report results for nivolumab (NIVO) plus gemcitabine-cis (GC) or GC alone in CheckMate 901.

Methods

In CheckMate 901 (NCT03036098), a global, open-label, randomized phase 3 trial, pts received NIVO 360 mg plus GC every 3 wk for up to 6 cycles followed by NIVO 480 mg every 4 wk until disease progression/unacceptable toxicity or up to a maximum of 2 years, or GC every 3 wk for up to 6 cycles. Stratification factors were programmed death ligand 1 status and liver metastasis. Primary endpoints were overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR). Objective response rate (ORR) per BICR was an exploratory endpoint.

Results

A total of 304 pts were randomized to each arm. With a median follow-up of 33.6 mo, both OS (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.63–0.96; P = 0.0171) and PFS (HR, 0.72; 95% CI, 0.59–0.88; P = 0.0012) were significantly improved with NIVO+GC vs GC (table). ORR and complete response (CR) rates were 57.6% and 21.7% with NIVO+GC vs 43.1% and 11.8% with GC. Median duration of CR (95% CI) was 37.1 (18.1–not estimable] mo for NIVO+GC vs 13.2 (7.3–18.4) mo with GC. Grade ≥ 3 treatment-related adverse events occurred in 61.8% of pts in the NIVO+GC arm and 51.7% of pts in the GC arm.

Conclusions

NIVO+GC demonstrated statistically significant and clinically meaningful improvements in OS and PFS vs GC alone as first-line treatment for mUC with no new toxicity signals. NIVO+GC is the first frontline concurrent checkpoint inhibitor + chemo combination to improve OS in this setting. These results support NIVO plus cis-based chemo as a new SOC for pts with mUC. (Table). Table: LBA7

Clinical trial identification

NCT03036098.

Editorial acknowledgement

Writing and editorial assistance were provided by Nicolette Belletier, PhD, of Parexel, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

M.S. van der Heijden: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Janssen, MSD, Seagen, Pfizer; Financial Interests, Institutional, Funding, Investigator-initiated trial: BMS, Roche, AstraZeneca, 4SC; Financial Interests, Institutional, Steering Committee Member, Local PI + SSC member: BMS, AstraZeneca, MSD, Seagen; Financial Interests, Institutional, Steering Committee Member, Local PI + study co-PI: Janssen; Financial Interests, Institutional, Local PI: GSK. G.P. Sonpavde: Financial Interests, Personal, Advisory Board: EMD Serono/Pfizer, Bristol Myers Squibb, Genentech, Merck, Sanofi, Seattle Genetics, Exelixis, Janssen, Bicycle Therapeutics, Immunomedics/Gilead, Scholar Rock, G1 Therapeutics, Loxo Oncology, Lucence, Tempus, Syapse; Financial Interests, Personal, Advisory Board, Editor of Bladder cancer virtual center of excellence for Practice Update: Elsevier; Financial Interests, Personal, Other, Member of data safety monitoring board: Mereo; Financial Interests, Personal, Other, Author of chapter: Uptodate; Financial Interests, Personal, Invited Speaker: Research to practice, Seattle Genetics, Gilead, Exelixis, Janssen; Financial Interests, Personal, Advisory Board, to develop a trial in bladder cancer: Servier Pharmaceuticals; Financial Interests, Institutional, Research Grant: Sanofi, Gilead, QED, Predicine, EMD Serono, Jazz Pharma; Non-Financial Interests, Principal Investigator, Steering committee of trial: Bristol Myers Squibb; Non-Financial Interests, Principal Investigator: G1 Therapeutics; Non-Financial Interests, Leadership Role, steering committee of trial: QED; Non-Financial Interests, Other, steering committee of trial: Merck; Other, Spouse employment: Myriad Genetics. T.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen; Financial Interests, Personal, Other, Sponsorship for Uromigos Podcast: Mashup Ltd; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bristol Myers Squibb, Exelixis, Ipsen, Merck, MSD, Seattle Genetics, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai. A. Necchi: Financial Interests, Institutional, Research Grant: Merck, AstraZeneca, Ipsen, BMS, Gilead; Financial Interests, Personal, Steering Committee Member: Roche, Janssen, Bayer, Astellas, AstraZeneca, Merck, Clovis Oncology; Financial Interests, Coordinating PI: Incyte; Financial Interests, Local PI: Pfizer; Non-Financial Interests, Leadership Role: Global society of Rare Genitourinary Tumors (GSRGT). M. Burotto: Financial Interests, Personal, Invited Speaker: BMS, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Merck. M. Schenker: Financial Interests, Personal and Institutional, Local PI, Payment for Clinical trials activities: AbbVie, Amgen, Astellas, AstraZeneca, BMS, BeiGene, Bioven, Clovis, Daiichi Sankyo, Eisai, GSK, Gilead, MSD, Merck Serono, Mylan, Novartis, Pfizer, Pharma Mar, Regeneron, Roche, Samsung Pharmaceutical, Sanofi. A. Bamias: Financial Interests, Personal, Invited Speaker: Ipsen, Debiopharm; Financial Interests, Personal, Advisory Board: BMS, MSD, AstraZeneca; Financial Interests, Steering Committee Member: Roche; Financial Interests, Institutional, Coordinating PI: Roche, BMS, MSD; Financial Interests, Institutional, Funding: AstraZeneca, Pfizer; Non-Financial Interests, Leadership Role: Hellenic GU Cancer Group. J. Bedke: Financial Interests, Personal, Advisory Board: AstraZeneca, Astellas, Eisai; Financial Interests, Personal, Advisory Board, Advisory Board and Speaker´s Bureau: BMS, Ipsen, MSD, Merck Serono, Pfizer, Roche, Janssen; Financial Interests, Institutional, Advisory Board: BMS, Pfizer; Financial Interests, Institutional, Local PI: AstraZeneca, Eisai, Novartis, Nektar; Financial Interests, Institutional, Coordinating PI: Astellas, BMS, MSD, Ipsen, Seagen, Pfizer, Roche; Financial Interests, Institutional, Steering Committee Member: BMS, MSD, Pfizer, Seagen; Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology. J. Oldenburg: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb, MSD, Pfizer, Roche, Astellas, AstraZeneca, Bayer, Eisai, Ipsen, Janssen-Cilaq; Financial Interests, Institutional, Coordinating PI: Bristol-Myers Squibb, MSD, Sanofi; Financial Interests, Institutional, Local PI: Bristol Myers Squibb. Y. Urun: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Janssen Oncology, Pfizer, Bristol-Myers Squibb, Roche, MSD; Financial Interests, Personal, Invited Speaker: Astellas, Janssen Oncology, pfizer, Bristol-Myers Squibb, Roche, Amgen; Financial Interests, Personal and Institutional, Local PI: Bristol-Myers Squibb, AstraZeneca, MSD, Janssen, Roche. B. Perez Valderrama: Financial Interests, Personal, Advisory Board: Pfizer, Astellas Pharma, Bristol-Myers-Squibb, Ipsen, EUSA Pharma, Merck, MSD, Astra-Zeneca, AAA; Financial Interests, Personal, Invited Speaker: Bristol-Myers-Squibb, Roche, Bayer, EUSA Pharma, MSD, Merck, Pfizer, Janssen, Astellas Pharma, AAA. Y. Tomita: Financial Interests, Personal, Invited Speaker: Astellas, BMS, Merck, Ono; Financial Interests, Institutional, Research Grant: Chugai, Ono; Non-Financial Interests, Advisory Board: Eisai, Ono. J. Filian: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb ; Financial Interests, Personal, Stocks or ownership: Bristol Myers Squibb. D. Purcea: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb ; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. F. Nasroulah: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. M.D. Galsky: Financial Interests, Personal, Advisory Board: Janssen, Merck, GSK, Eli Lilly, Astellas, Genentech, Bristol Myers Squibb, Pfizer, EMD Serono, AstraZeneca, SeaGen, Incyte, Alligator, AbbVie, Asieris, Bicycle, Gilead, Curis, Fujifilm; Financial Interests, Personal, Other, Consultant: Rappta Therapeutics; Financial Interests, Institutional, Steering Committee Member: Merck, Genentech, Bristol Myers Squibb; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Jazz; Financial Interests, Institutional, Local PI: Seagen. All other authors have declared no conflicts of interest.