– Median progression-free survival was not yet reached with the combination of cabozantinib, nivolumab and ipilimumab versus 11.3 months with nivolumab combined with ipilimumab –
Reno, Nevada (UroToday.com) -- Exelixis, Inc. announced detailed results from COSMIC-313, an ongoing phase 3 pivotal trial evaluating the combination of cabozantinib (CABOMETYX®), nivolumab and ipilimumab versus the combination of nivolumab and ipilimumab in patients with previously untreated advanced intermediate- or poor-risk renal cell carcinoma (RCC). The data, including detailed results of the primary endpoint of progression-free survival (PFS), are being presented during the Presidential Symposium III (LBA8) on Monday, September 12 at 4:30 p.m. CEST at the 2022 European Society of Medical Oncology (ESMO) Congress.
“I look forward to presenting detailed results from COSMIC-313, which provide a clear look at the efficacy and safety profile for this combination of cabozantinib plus dual checkpoint inhibition,” said Toni Choueiri, M.D., Director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute and the Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School. “As the first trial with a control arm of nivolumab plus ipilimumab, COSMIC-313 was designed to answer an important question of whether adding cabozantinib to dual checkpoint inhibition can improve outcomes for this poor- and intermediate-risk renal cell carcinoma patient population. I am pleased that the trial demonstrated a significant progression-free survival benefit in patients receiving the triplet combination.”Eligible patients in the trial had intermediate- or poor-risk advanced RCC according to the International Metastatic RCC Database Consortium with a clear-cell component and Karnofsky performance status ≥70%. Of the 855 patients that were randomized, 75% were intermediate-risk and 25% were poor-risk.
As previously announced, the primary endpoint of PFS per Response Evaluation Criteria in Solid Tumors version 1.1, as assessed by Blinded Independent Radiology Committee (BIRC), demonstrated that cabozantinib in combination with nivolumab and ipilimumab significantly reduced the risk of disease progression or death compared with the combination of nivolumab and ipilimumab (hazard ratio: 0.73; 95% confidence interval [CI]: 0.57-0.94; P=0.013). At a prespecified interim analysis for the secondary endpoint of overall survival (OS), the combination of cabozantinib, nivolumab and ipilimumab versus the combination of nivolumab and ipilimumab did not demonstrate a significant benefit. Therefore, the trial will continue to the next analysis of OS.
“We are pleased to share a more detailed picture of this triplet combination of cabozantinib, nivolumab and ipilimumab in patients with advanced kidney cancer at ESMO this year, reinforcing our longstanding commitment to this patient community,” said Vicki L. Goodman, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “We plan to discuss these findings from COSMIC-313 with U.S. regulators and will provide further updates, including the analysis of overall survival, when available.”
The new results being presented at the 2022 ESMO Congress demonstrate that median PFS was not reached for the combination of cabozantinib, nivolumab and ipilimumab (95% CI: 14.0-not estimable) and was 11.3 months for the combination of nivolumab and ipilimumab (95% CI: 7.7-18.2). Objective response rates in the PFS intent-to-treat population as assessed by BIRC were 43% (95% CI: 37.2-49.2) and 36% (95% CI: 30.1-41.8), respectively. The median duration of response was not reached in either treatment arm. PFS subgroup analyses will also be presented.
The safety profile observed in the trial was reflective of the known safety profiles for each single agent as well as the combination regimens used in this study. No new safety signals were identified. Grade 3/4 treatment-emergent adverse events (AEs) occurred in 73% of patients treated with the combination of cabozantinib, nivolumab and ipilimumab and in 41% of patients treated with the combination of nivolumab and ipilimumab. Three patients (1%) in each arm had a grade 5 treatment-related AE. Discontinuation of all treatments due to treatment-emergent AEs occurred in 12% and 5% of patients, respectively.
Source: "Exelixis Announces Detailed Results From Phase 3 COSMIC-313 Pivotal Trial In Patients With Previously Untreated Advanced Kidney Cancer At ESMO 2022 | Exelixis, Inc.". 2022. Exelixis, Inc.