Opdivo® (nivolumab) in Combination with CABOMETYX® (cabozantinib) Shows Durable Survival with Over Three Years of Follow-Up in the CheckMate -9ER Trial in First-Line Advanced Renal Cell Carcinoma

  • Data to be featured at ASCO GU 2023 demonstrate continued overall survival, progression-free survival and objective response rate benefits with Opdivo in combination with CABOMETYX compared to sunitinib, regardless of IMDC risk score
  • These three-year data – with a median follow-up of 44 months – from CheckMate -9ER represent the longest reported follow-up in any Phase 3 trial with an immunotherapy-tyrosine kinase inhibitor regimen in this population
  • In an exploratory biomarker analysis, median progression-free survival and overall survival were improved with the combination of Opdivo and CABOMETYX regardless of PD-L1 status

Reno, Nevada (UroToday.com) -- Bristol Myers Squibb and Exelixis, Inc. announced three-year (36.5 months minimum; 44.0 months median) follow-up results from the Phase 3 CheckMate -9ER trial, demonstrating sustained survival and response rate benefits with the combination of Opdivo® (nivolumab) and CABOMETYX® (cabozantinib) versus sunitinib in the first-line treatment of advanced renal cell carcinoma (RCC). 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.

“Despite the progress made through science and medicine, there remains a need for treatment options that can durably extend survival for patients with metastatic renal cell carcinoma, especially for those classified as higher risk,” said Mauricio Burotto, M.D., medical director, Bradford Hill Clinical Research Center, Santiago, Chile. “With these updated results from CheckMate -9ER, we’ve now seen nivolumab in combination with cabozantinib durably extend survival and sustain response benefits compared to sunitinib for over three years, regardless of patients’ risk classification. These results reinforce the importance of this immunotherapy-tyrosine kinase inhibitor regimen for patients and its potential to help change survival expectations for patients with this challenging cancer.”
Abstract #603: Nivolumab plus cabozantinib vs sunitinib for first-line treatment of advanced renal cell carcinoma (aRCC): 3-year follow-up from the phase 3 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:

  • 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.
  • 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).
  • 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.
  • 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 ≥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 3 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 ≥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.

“We have a strong heritage of bringing immunotherapy-based combinations to patients with advanced renal cell carcinoma and transforming patient outcomes with Opdivo-based combinations across several cancer types,” said Dana Walker, M.D., M.S.C.E., vice president, development program lead, genitourinary cancers, Bristol Myers Squibb. “The updated data from CheckMate -9ER further reinforce the use of Opdivo in combination with CABOMETYX for the first-line treatment of patients with advanced renal cell carcinoma. We remain committed to collaboration across the scientific community and our ongoing exploration of combination approaches with our proven cancer agents in the pursuit of solutions that may help improve long-term outcomes for as many patients as possible.”

“With forty-four months median follow-up, the compelling survival benefit further reinforces the value of the CABOMETYX and Opdivo combination regimen as a first-line option for patients with advanced kidney cancer,” said Vicki L. Goodman, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “We are pleased to share these long-term findings at ASCO GU and remain steadfast in our longstanding commitment to improving outcomes for patients living with advanced kidney cancer.”

Bristol Myers Squibb and Exelixis thank the patients and investigators involved in the CheckMate -9ER clinical trial.

Source: Bristol Myers Squibb and Exelixis, Inc. 2023. Opdivo® (nivolumab) in Combination with CABOMETYX® (cabozantinib) Shows Durable Survival with Over Three Years of Follow-Up in the CheckMate -9ER Trial in First-Line Advanced Renal Cell Carcinoma [Press release]. https://ir.exelixis.com/news-releases/news-release-details/opdivor-nivolumab-combination-cabometyxr-cabozantinib-shows-0.