Adjuvant nivolumab monotherapy vs placebo for localized renal cell carcinoma at high risk of relapse after nephrectomy: Results from Part B of the randomized, phase 3 CheckMate 914 trial.
Authors: Motzer Robert J. , Bex Axel , Russo Paul , Tomita Yoshihiko , Cutuli Hernan , Rojas Carlos , Gross-Goupil Marine , Schinzari Giovanni , Melichar Bohuslav , Barthelemy Philippe , Ruiz Garcia Abraham , Sosman Jeffrey A. , Grimm Marc-Oliver , Goh Jeffrey C. , Suárez Cristina , Kollmannsberger Christian K. , Simsek Burcin , Spiridigliozzi Julia , Lee Chung-Wei , Grünwald Viktor 
Published: January 2024

LBA358 Background: CheckMate 914 (NCT03138512) is a phase 3, randomized, double-blind, multicenter, 2-part trial evaluating adjuvant NIVO plus ipilimumab (NIVO+IPI) vs PBO (Part A) or adjuvant NIVO monotherapy vs PBO (and NIVO monotherapy vs NIVO+IPI to assess the contribution of components; Part B) designed in sequence in mutually exclusive patients (pts) with localized RCC at high risk of post-nephrectomy relapse. Results from Part A at 37.0 months median study follow-up (range, 15.4–58.0) showed no disease-free survival (DFS) benefit for adjuvant NIVO+IPI vs PBO in the overall study population ( Lancet 2023;401:821–832). We report primary analyses for Part B of the trial. Methods: Pts eligible for CheckMate 914 included those undergoing radical or partial nephrectomy between 4 and 12 weeks before randomization with negative surgical margins; with predominantly clear cell histology (with or without sarcomatoid features); pathological TNM stage T2a (grade [G] 3/4) N0M0, T2b-T4 (any G) N0M0, or any T (any G) N1M0; and no evidence of residual disease or distant metastases (M0). Pts in Part B were randomized 2:1:1 to NIVO (240 mg every 2 weeks × 12) plus IPI PBO, NIVO (240 mg every 2 weeks × 12) plus IPI (1 mg/kg every 6 weeks × 4), or matching PBO, and stratified by pathological TNM stage and type of nephrectomy. Treatment was planned for 24 weeks (approximately 5.5 months) or until disease recurrence/unacceptable toxicity. The primary endpoint for Part B is DFS per blinded independent central review (BICR) for NIVO monotherapy vs PBO. Secondary endpoints include safety of NIVO monotherapy. Results: In total,619 pts were randomized to NIVO monotherapy (n = 411) or PBO (n = 208). With 27.0 months median study follow-up (range, 18.0–42.4), the primary efficacy endpoint of DFS per BICR with NIVO monotherapy vs PBO was not met (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.62–1.21; P = 0.3962). Median DFS was not reached in either arm; DFS probabilities were 83.3% vs 78.2% (at 12 months) and 78.4% vs 75.4% (at 18 months), respectively. The HR for DFS per investigator was 0.80 (95% CI, 0.58–1.12; P = 0.1936). Median (Q1, Q3) treatment duration was 5.1 (5.1, 5.3) months with NIVO monotherapy and 5.1 (5.1, 5.2) months with PBO. Any-grade treatment-related adverse events (AEs) were reported in 72.5% vs 51.7% of pts treated with NIVO monotherapy (n = 408) vs PBO (n = 207), and grade 3–4 treatment-related AEs were reported in 8.8% vs 1.9%, respectively. Any-grade treatment-related AEs led to discontinuation in 9.6% and 1.0% of pts in the NIVO monotherapy and PBO arms, respectively. Conclusions: Part B of the CheckMate 914 trial of NIVO monotherapy 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 monotherapy was consistent with its known profile in advanced RCC. Clinical trial information: NCT03138512 .