Opdivo + Cabometyx shows durable survival with over three years of follow-up in the CheckMate -9ER trial in first-line advanced renal cell carcinoma

Additionally, a biomarker analysis showed that improvements in median progression-free survival (PFS) and overall survival (OS) were sustained with the combination of Opdivo and Cabometyx regardless of PD-L1 status. These updated results will be featured in one oral and one poster presentation at the American Society of Clinical Oncology (ASCO) 2023 Genitourinary Cancers Symposium from February 16-18, 2023.

Abstract #603: Nivolumab plus cabozantinib vs sunitinib for first-line treatment of advanced renal cell carcinoma (aRCC): 3-year follow-up from the phase III CheckMate -9ER trial (Burotto, et. al.. With a median follow-up of 44.0 months (36.5 months minimum), Opdivo in combination with Cabometyx (n=323) continued to show superior OS, PFS, objective response rate (ORR), duration of response (DoR) and complete response (CR) rates versus sunitinib (n=328). No new safety signals were seen with extended follow-up. Within the full study population: i. OS: Treatment with Opdivo in combination with Cabometyx continued to show a 30% reduction in the risk of death (Hazard Ratio [HR] 0.70; 95% Confidence Interval [CI]: 0.56 to 0.87), and improvement in median OS vs. sunitinib (49.5 months vs. 35.5 months, respectively). Additionally, median OS improved by 11.8 months since the previous data cut at 32.9 months median follow-up. ii. PFS: PFS benefits were sustained, with the combination continuing to double median PFS vs. sunitinib (16.6 months vs. 8.4 months, respectively; HR 0.58; 95% CI: 0.48 to 0.71). iii. ORR and DoR: ORR benefits were maintained, with nearly twice as many patients responding to Opdivo in combination with Cabometyx vs. sunitinib (55.7% vs. 28.4%). Responses also continued to be more durable with the combination, with a median DoR of 23.1 months compared to 15.2 months with sunitinib. iv. CR: CR rates were also sustained, with 12.4% of those treated with Opdivo in combination with Cabometyx having a CR vs. 5.2% of those treated with sunitinib.

Safety: 97% of patients treated with Opdivo in combination with Cabometyx experienced a treatment-related adverse event (TRAE) of any grade compared to 93% of patients treated with sunitinib; 67% vs. 55% had a grade greater than 3 TRAE, respectively.Results were also assessed by the following International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores: favorable, intermediate, intermediate/poor and poor. Benefits were seen with Opdivo in combination with Cabometyx across all efficacy measures (OS, PFS, ORR and CR), regardless of IMDC risk.

Abstract #608: Biomarker analysis from the phase III CheckMate 9ER trial of nivolumab + cabozantinib v sunitinib for advanced renal cell carcinoma (aRCC) (Choueiri, et. al.). In an exploratory post-hoc analysis from CheckMate -9ER with 44.0 months median follow-up, improvements were observed in both median PFS and OS with Opdivo in combination with Cabometyx regardless of PD-L1 status. PFS and OS were evaluated by tumor PD-L1 expression (<1% or greater than 1%), cd8% (low, medium, high by tertiles), and cd8 topology phenotype (cold, excluded, inflamed), and assessed for association using kaplan-meier (km) methods with log-rank test (pd-l1 and cd8), and cox proportional hazard (cox ph) models (cd8). biomarkers previously found to be predictive of anti-pd-l1 + anti-vegf outcomes, including established gene expression signatures, were not necessarily predictive of efficacy with anti-pd-1 + anti-vegf targeted therapy, suggesting that key determinants of response to anti-pd-1 vs. anti-pd-l1 therapies may differ.></1%>

About CheckMate -9ER: CheckMate -9ER is an open-label, randomized, multi-national Phase III trial evaluating patients with previously untreated advanced or metastatic renal cell carcinoma (RCC). A total of 651 patients (23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1 less than 1%) were randomized to receive Opdivo plus Cabometyx (n=323) vs. sunitinib (n=328). The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS) and objective response rate (ORR). The primary efficacy analysis is comparing the doublet combination vs. sunitinib in all randomized patients. The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co. and co-funded by Exelixis, Inc., Ipsen Pharma SAS and Takeda Pharmaceutical Company Limited.