Bristol Myers Squibb (NYSE: BMY) and Exelixis, Inc. (NASDAQ: EXEL) today announced the first presentation of results from the pivotal Phase 3 CheckMate -9ER trial, in which Opdivo® (nivolumab) in combination with CABOMETYX® (cabozantinib) demonstrated significant improvements across all efficacy endpoints, including overall survival (OS), in previously untreated advanced renal cell carcinoma (RCC). Opdivo in combination with CABOMETYX reduced the risk of death by 40% vs. sunitinib (Hazard Ratio [HR] 0.60; 98.89% Confidence Interval [CI]: 0.40 to 0.89; p=0.0010; median OS not reached in either arm). In patients receiving Opdivo in combination with CABOMETYX, median progression-free survival (PFS), the trial’s primary endpoint, was doubled compared to those receiving sunitinib alone: 16.6 months vs. 8.3 months, respectively (HR 0.51; 95% CI: 0.41 to 0.64; p<0.0001).

In addition, Opdivo in combination with CABOMETYX demonstrated a superior objective response rate (ORR), with twice as many patients responding compared to sunitinib (56% vs. 27%), and 8% vs. 5% achieved a complete response. Opdivo in combination with CABOMETYX was associated with a longer duration of response than sunitinib, with a median duration of 20.2 months vs. 11.5 months. All of these key efficacy results were consistent across the pre-specified International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk and PD-L1 subgroups.

Opdivo combined with CABOMETYX was well tolerated and reflected the known safety profiles of the immunotherapy and tyrosine kinase inhibitor (TKI) components in previously untreated advanced RCC. The incidence of treatment-related adverse events (TRAEs), including any-grade and high-grade TRAEs, was slightly higher for Opdivo in combination with CABOMETYX vs. sunitinib (97% vs. 93% for any-grade; 61% vs. 51% for grade 3 and higher), with a low rate of treatment-related discontinuations (6% for Opdivo only, 7% for CABOMETYX only and 3% for both Opdivo and CABOMETYX vs. 9% for sunitinib). Patients treated with Opdivo in combination with CABOMETYX reported significantly better health-related quality of life than those treated with sunitinib at most time points, according to National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) Kidney Symptom Index 19 (FKSI-19) scores.

These results (Presentation #696O_PR) will be featured as a Proffered Paper during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Virtual Congress 2020, on September 19, 2020 from 19:34-19:46 CEST.

“While we’ve seen considerable progress in the treatment of metastatic renal cell carcinoma, we must continue to research new options to help more patients achieve positive outcomes,” said Dr. Toni Choueiri, 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. “The CheckMate -9ER data demonstrate meaningful efficacy benefits with nivolumab plus cabozantinib, which significantly improved overall survival and doubled progression-free survival and objective response rate with consistent effects observed across pre-specified subgroups. These results, along with a favorable tolerability profile and superior health-related quality of life, highlight this regimen’s potential importance among combinations of immunotherapies and tyrosine kinase inhibitors.”

Based on these efficacy and safety results from CheckMate -9ER, Bristol Myers Squibb and Exelixis’ partner Ipsen, which has exclusive rights to commercialize and develop CABOMETYX outside of the U.S. and Japan, each submitted type II variation applications for Opdivo plus CABOMETYX to the European Medicines Agency (EMA). On September 12, the EMA validated the type II variations, confirming the submissions are complete and beginning the EMA’s centralized review process. In addition, Bristol Myers Squibb and Exelixis recently completed their respective U.S. Food and Drug Administration (FDA) submissions for Opdivo in combination with CABOMETYX and, along with their partners, plan to discuss the CheckMate -9ER data with regulatory authorities across the world.

“These data are yet another example of the potential of immunotherapy-based combinations to meaningfully extend survival for patients with advanced cancers, strengthening our legacy in the genitourinary space,” said Nick Botwood, M.D., vice president, interim head, Oncology Development, Bristol Myers Squibb. “Opdivo was the first immune checkpoint inhibitor approved as a second-line treatment for advanced renal cell carcinoma, and then, with the addition of Yervoy, the first dual immunotherapy approved for certain patients in the first-line setting. With the promising results from CheckMate -9ER, we hope to bring the highly efficacious combination of Opdivo and CABOMETYX to patients with advanced renal cell carcinoma for whom an immunotherapy plus tyrosine kinase inhibitor regimen is chosen.”

“Considering the scientific and clinical evidence suggesting CABOMETYX uniquely creates a more immune-permissive tumor environment that may allow for synergistic antitumor activity when combined with Opdivo, we’re encouraged by the significant and consistent efficacy benefits shown in Checkmate -9ER for the first-line treatment of advanced kidney cancer, including all IMDC risk groups and PD-L1 status,” said Gisela Schwab, M.D., president, product development and medical affairs and chief medical officer, Exelixis. “The favorable efficacy and tolerability profile suggests that, if approved, CABOMETYX in combination with Opdivo would be an important new option for patients with advanced kidney cancer.”

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

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