LBA4 - Adjuvant nivolumab plus ipilimumab (NIVO+IPI) vs placebo (PBO) for localized renal cell carcinoma (RCC) at high risk of relapse after nephrectomy: Results from the randomized, phase III CheckMate 914 trial

Background

CheckMate 914 (NCT03138512) is a phase III, randomized, double-blind, multicenter, 2-part trial evaluating NIVO+IPI vs PBO (part A) or NIVO monotherapy vs NIVO+IPI vs PBO (part B) in mutually exclusive patients (pts) with localized RCC at high risk of post-nephrectomy relapse. We report the primary analysis for part A of this trial.

Methods

CheckMate 914 key inclusion criteria: radical or partial nephrectomy with negative surgical margins > 4 and ≤ 12 weeks before randomization; predominant clear cell histology; pathological TNM stage T2a (grade [G] 3 or 4) N0M0, T2b (any G) N0M0, T3 (any G) N0M0, T4 (any G) N0M0, or any T (any G) N1M0; and no clinical/radiological evidence of residual disease or distant metastases. Pts were randomized 1:1 to NIVO 240 mg Q2W (× 12 doses) + IPI 1 mg/kg Q6W (× 4 doses) or equivalent PBO for 24 weeks or until disease recurrence/unacceptable toxicity. Stratification factors: TNM stage and type of nephrectomy. Primary endpoint: disease-free survival (DFS) per blinded independent central review; secondary endpoints include overall survival and safety.

Results

816 pts were randomized to NIVO+IPI (n = 405) vs PBO (n = 411). With 37.0 months of median follow-up (range, 15.4–58.0), the primary efficacy endpoint of DFS was not met (HR, 0.92; 95% CI, 0.71–1.19; P = 0.5347). Median DFS was not reached with NIVO+IPI and 50.7 months with PBO; DFS probabilities at 24 months were 76.4% and 74.0%, respectively. Median (Q1, Q3) treatment duration was 5.1 (2.8, 5.3) months and 5.1 (5.1, 5.3) months, respectively. Any-grade treatment-related adverse events (AEs) were reported in 88.9% vs 56.8% of pts treated with NIVO+IPI vs PBO; grade ≥ 3 treatment-related AEs were reported in 28.5% vs 2.0%, respectively. Treatment-related AEs led to discontinuation of NIVO+IPI in 29.0% of pts and of PBO in 1.0% of pts.

Conclusions

The CheckMate 914 trial of NIVO+IPI vs PBO in pts with localized RCC at high risk of relapse after nephrectomy did not meet the primary endpoint of DFS. Safety of NIVO+IPI was consistent with its known profile in advanced RCC, although the rate of discontinuation due to treatment-related AEs was higher with adjuvant NIVO+IPI vs PBO in this trial.

Clinical trial identification

NCT03138512.

Editorial acknowledgement

Professional medical writing assistance was provided by Richard Daniel, PhD, of Parexel, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

R.J. Motzer: Financial Interests, Personal, Advisory Board: AstraZeneca, Aveo, Aveo Pharmaceuticals, Eisai, EMD Serono, Exelixis, Genentech/Roche, Incyte, Lilly Oncology, Merck, Novartis, Pfizer; Financial Interests, Personal, Coordinating PI, funding for trial conduct from sponsor to my employer MSKCC: Aveo, BMS, Eisai, Exelixis, Genentech/Roche, Merck, Pfizer. V. Gruenwald: Financial Interests, Personal, Advisory Board: Apogepha, AstraZeneca, BMS, Debiopharm, Eisai, EUSA Pharm, Merck Serono, MSD, Nanobiotix, Oncorena, PCI Biotech, Pfizer, Roche; Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, BMS, Eisai, Ipsen, Janssen-Cilag, Merck Serono, MSD, Novartis, Pfizer, Roche; Financial Interests, Personal, Stocks/Shares: AstraZeneca, BMS, MSD, Seattle Genetics; Financial Interests, Institutional, Research Grant: BMS, Ipsen, MSD; Non-Financial Interests, Personal, Steering Committee member: BMS; Financial Interests, Personal and Institutional, Steering Committee member: Eisai, Novartis; Non-Financial Interests, Institutional, Steering Committee member: Ipsen; Non-Financial Interests, Personal, Research Grant: Pfizer; Non-Financial Interests, Personal, Trial Chair: PharmaMar. 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. S. Buti: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Ipsen, MSD, Novartis, Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Ipsen, MSD, Novartis; Financial Interests, Personal, Expert Testimony: MSD, Pierre-Fabre; Non-Financial Interests, Institutional, Local PI: AstraZeneca, BMS, Ipsen; Non-Financial Interests, Institutional, Coordinating PI: BMS; Non-Financial Interests, Institutional, Research Grant: Novartis; Non-Financial Interests, Member of the panel for kidney cancer guidelines: AIOM (Italian Association of Medical Oncology); Non-Financial Interests, Member and Coordinator of the rate tumors group: Meet-URO group (Italian Network for Research in Urologic Oncology). P. Barthelemy: Financial Interests, Personal, Research Grant: BMS, Ipsen, MSD, Pfizer, AstraZeneca, Janssen; Financial Interests, Personal, Consulting fees: BMS, Ipsen, MSD, Merck, Pfizer, Janssen-Cilag, Astellas, Amgen; Financial Interests, Personal, Speaker’s Bureau: BMS, Ipsen, MSD, Merck, Pfizer, Janssen-Cilag, Astellas, Bayer, Sanofi, Seagen, Novartis; Financial Interests, Personal, Travel support: BMS, Ipsen, MSD, Merck, Pfizer, Janssen-Cilag, Astellas, Sanofi, Seagen, Novartis. J.C.H. Goh: Financial Interests, Personal, Advisory Board, Prior member of the BMS RCC Advisory Board: BMS; Financial Interests, Personal, Advisory Board, Uterine Cancer Advisory Board: GSK; Financial Interests, Personal, Chairing RCC meeting: Ipsen; Financial Interests, Personal, Invited Speaker, Speaking @ MSD sponsored event on Gynaecological cancer: MSD; Financial Interests, Personal, Asia-Pacific Advisory Board member for prostate cancer: AstraZeneca; Financial Interests, Personal, Stocks/Shares, Private Cancer Centres in Australia: ICON Cancer Centres; Non-Financial Interests, Institutional, Funding, Funding for phase II metastatic cervical cancer trial: BeiGene; Financial Interests, Principal Investigator, local PI for CheckMate-914, CheckMate-9KD Trial, CheckMate-7DX & CheckMate-9ER trials: BMS. J. Lattouf: Financial Interests, Personal, Advisory Board, Regional consultation group on bladder cancer (Québec): BMS; Financial Interests, Personal, Advisory Board, Assessment of prostate cancer practices: Knights; Financial Interests, Institutional, Invited Speaker, A presentation for community urologists about salvage therapy inprostate cancer: Tersera; Financial Interests, Personal, Advisory Board, BCG use in bladder cancer: Verity; Financial Interests, Institutional, Other, Local PI Research fees for the BMS914 trial: BMS; Financial Interests, Member: AUA, Candian Uro-Oncology Group, Canadian Urological Associations. B. Escudier: Financial Interests, Personal, Advisory Board: Pfizer, BMS, Ipsen, Aveo, Eisai. S. George: Financial Interests, Personal, Advisory Board, Advisor/consultant: Aveo, Bayer, BMS, Corvus, Eisai, EMD Serono, Exelixis, Merck, Pfizer, QED Therapeutics, Sanofi/Genzyme, Seattle Genetics; Non-Financial Interests, Personal, Local PI: Agensys, Aravive, Aveo, Bayer, BMS, Calithera, Corvus, Eisai, Exelixis, Gilead, Merck, Novartis, Pfizer, Seattle Genetics, Surface Oncology. B. Shuch: Financial Interests, Personal, Advisory Board: Genentech, Merck; Personal, Consultant for new device testing: J&J; Financial Interests, Personal, Invited Speaker, for Welireg: Merck; Personal, Consulted on genomic testing in kidney cancer: Veracyte; Non-Financial Interests, Institutional, Research Grant, Research on CAR T target: Allogene; Non-Financial Interests, Institutional, Coordinating PI Research on microbiome: Rebiotix. B. Simsek: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. J. Spiridigliozzi: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. A. Chudnovsky: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. A. Bex: Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Principal Investigator, Steering Committee member: BMS,Roche Genentech; Financial Interests, Advisory Role: International Kidney Cancer Coalition, KCA. All other authors have declared no conflicts of interest.