Phase III CheckMate-9ER Trial Meets Primary Endpoint in Advanced RCC Trial

The pivotal phase III trial CheckMate-9ER evaluating nivolumab (Opdivo) in combination with cabozantinib (Cabometyx), compared to sunitinib (Sutent), in previously untreated advanced or metastatic renal cell carcinoma (RCC) met its primary endpoint of progression-free survival (PFS) at final analysis, according to Bristol Myers Squib and Exelixis, the developers of the agents.¹

“The positive topline results from the Phase III CheckMate-9ER trial evaluating Opdivo in combination with Cabometyx build on our understanding of Opdivo-based regimens, and we look forward to working with global health authorities to help bring this new combination regimen to previously untreated patients, a population that despite recent advances, remains in need of additional therapeutic options that extend survival,” Brian Lamon, PhD, development lead of genitourinary cancers at Bristol Myers Squibb, said in a press release.

The combination of the immunotherapy and tyrosine kinase inhibitor also met its secondary endpoints of overall survival (OS) at pre-specified interim analysis, and objective response rate (ORR). Additional secondary outcomes included incidence of adverse events (AEs) and incidence of serious AEs. 

“Given the growing body of data showing that Cabometyx may create a more immune-permissive tumor environment that may enhance response to immune checkpoint inhibitors, we have been eagerly awaiting the results for the combination of cabozantinib and nivolumab in previously untreated renal cell carcinoma,” Gisela Schwab, MD, president of product development and medical affairs and chief medical officer at Exelixis, said in a press release. “We’re delighted that the trial met its primary endpoint of progression-free survival as well as the secondary endpoints of overall survival and objective response rate, demonstrating consistent benefit for the combination in previously untreated renal cell carcinoma patients.”

The open-label, multi-national phase III trial randomized a total of 701 patients with previously untreated advanced or metastatic RCC in a 1:1 fashion to either nivolumab and cabozantinib or sunitinib. Moreover, the safety profiles of both nivolumab and cabozantinib reflected the known safety profiles in first line RCC. The primary efficacy analysis will be comparing the doublet combination versus sunitinib in all randomized patients.

“The results from the pivotal CheckMate-9ER trial clearly demonstrate the combination of cabozantinib plus nivolumab provides a clinically meaningful benefit in the key efficacy measures of progression-free survival and overall survival for previously untreated kidney cancer patients,” Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School, said in a press release. “Preliminary assessment of the data shows the combination of a 40 mg dose of cabozantinib plus nivolumab demonstrated a favorable safety profile. If approved, this combination may become an important new first-line option for patients with metastatic renal cell carcinoma. We look forward to presenting detailed results at an upcoming congress.”

Cabozantinib was approved by the FDA in December 2017 for previously untreated patients with advanced RCC based on results from the CABOSUN trial, which evaluated cabozantinib in comparison with sunitinib.² Further, the FDA approved nivolumab in April 2018 for use in combination with ipilimumab as a frontline treatment for intermediate- and poor-risk patients with advanced RCC based on the phase III CheckMate-214 trial.³

References:

1. Bristol Myers Squibb and Exelixis Announce Positive Topline Results from Pivotal Phase 3 CheckMate-9ER Trial Evaluating Opdivo (nivolumab) in Combination with Cabometyx (cabozantinib) in Previously Untreated Advanced Renal Cell Carcinoma [news release]. Princeton, NJ and Alameda, CA. Published April 20, 2020. news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-and-exelixis-announce-positive-topline-re. Accessed April 20, 2020. 

2. FDA grants regular approval to Cabometyx for first-line treatment of advanced renal cell carcinoma [news release]. FDA. Published December 19, 2017. fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-cabometyx-first-line-treatment-advanced-renal-cell-carcinoma. Accessed April 20, 2020.

3. FDA approves nivolumab plus ipilimumab combination for intermediate or poor-risk advanced renal cell carcinoma [news release]. FDA. Published April 16, 2018. fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-plus-ipilimumab-combination-intermediate-or-poor-risk-advanced-renal-cell. Accessed April 20, 2020.