Opdivo® (nivolumab) in Combination with CABOMETYX® (cabozantinib) Demonstrates Significant Survival Benefits in First-Line Treatment of Advanced Renal Cell Carcinoma

September 21, 2020 News /Bio ValleyBIOON/ -- Bristol-Myers Squibb (BMS) and its partner Exelixis, Inc. recently announced at the 2020 European MedicalTumorResults from the pivotal Phase III CheckMate -9ER trial of Opdivo (nivolumab) in combination with the targeted anticancer agent Cabometyx (cabozantinib) as first-line treatment for advanced renal cell carcinoma (RCC) were presented at the European Society for Medical Oncology (ESMO) Virtual Congress.

The results showed that in patients with advanced RCC who had not previously received treatment, compared with the first-line standard-of-care drug Sutent (generic name: sunitinib, a tyrosine kinase inhibitor,PfizerCompared with the development), the "immunotherapy + targeted therapy" regimen of Opdivo + Cabometyx demonstrated significant improvements across all efficacy endpoints,including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR).

The specific data are as follows: (1) In terms of OS, the Opdivo + Cabometyx group showed a significant 40% reduction in the risk of death compared with the Sutent group (HR = 0.60; 98.89% CI: 0.40–0.89; p = 0.0010), and the median OS was not reached in either group. (2) For the primary endpoint PFS, the Opdivo + Cabometyx group demonstrated a doubling of PFS compared with the Sutent group (median PFS: 16.6 months vs. 8.3 months; HR = 0.51; 95% CI: 0.41–0.64; p < 0.0001). (3) In terms of ORR, the Opdivo + Cabometyx group achieved twice the rate of the Sutent group (56% vs. 27%), with a higher complete response (CR) rate (8% vs. 5%). (4) Regarding DOR, the Opdivo + Cabometyx group had a longer duration than the Sutent group (median DOR: 20.2 months vs. 11.5 months). Notably,All these key efficacy outcomes were consistent across the prespecified International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk and PD-L1 subgroups.

In the study, the combination of Opdivo and Cabometyx was well tolerated, reflecting the known safety profile of immunotherapy and tyrosine kinase inhibitors (TKIs) in the first-line treatment of advanced renal cell carcinoma (RCC). Based on the National Comprehensive Cancer Network–Functional Assessment of Cancer Therapy Kidney Symptom Index 19 (NCCN-FACT FKSI-19) scores, patients treated with Opdivo plus Cabometyx demonstrated significantly better health-related quality of life than those treated with Sutent at most time points.

Based on the study results, partners of BMS and ExelixisipsClass II variation applications for Opdivo and Cabometyx have been submitted to the European Medicines Agency (EMA) respectively. On September 12, the EMA validated the Class II variation applications, confirmed that the submitted documentation was complete, and initiated the EMA centralized review procedure. In addition, BMS and Exelixis recently completed submissions to the U.S.FDASubmit respective applications.

BMSTumorDr. Nick Botwood, Interim Head of Development, stated: “These data are another example of how immunotherapy-based combination regimens meaningfully extend survival in patients with advanced cancer, reinforcing our established legacy in the genitourinary space. Opdivo was the first immune checkpoint inhibitor approved as a second-line treatment for advanced RCC; subsequently, Opdivo plus Yervoy became the first dual immunotherapy approved for the first-line treatment of certain patients with advanced RCC. With the robust efficacy results from the CheckMate-9ER study, we aim to bring the highly effective combination of Opdivo and Cabometyx to the population of patients with advanced RCC.”

Kidney Cancer (Image source: vecteezy.com)

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, causing more than 140,000 deaths worldwide each year. The incidence of RCC in men is approximately twice that in women, with the highest rates observed in North America and Europe. Globally,DiagnosisFor patients with metastatic or advanced renal cell carcinoma, the 5-year survival rate is only 12.1%. In recent years, despite some therapeutic advances, additional treatment options are still needed to prolong survival.

The results of the CheckMate-9ER study clearly demonstrate that the first-line treatment of patients with advanced or metastatic renal cell carcinoma (RCC) with the Opdivo and Cabometyx “immunotherapy + targeted therapy” combination regimen leads to clinically meaningful improvements in key efficacy endpoints, including progression-free survival (PFS) and overall survival (OS). Furthermore, the combination of Opdivo and Cabometyx exhibits a favorable safety profile. If approved, the Opdivo and Cabometyx “immunotherapy + targeted therapy” combination will provide an important new first-line treatment option for patients with previously untreated advanced or metastatic RCC.

The active pharmaceutical ingredient of Cabometyx is cabozantinib, a tyrosine kinase inhibitor (TKI) that exerts antitumor effects by selectively inhibiting the MET, VEGFR2, and RET signaling pathways, thereby killingTumorcells, reducing metastasis and inhibiting angiogenesis. In the United States, the European Union, Japan, and other countries and regions worldwide, Cabometyx has been approved for the treatment of patients with advanced renal cell carcinoma (RCC), as well as patients with hepatocellular carcinoma (HCC) who have previously been treated with sorafenib.

In the treatment of renal cell carcinoma (RCC), the approved indications for Opdivo are: (1) for patients with advanced RCC who have previously received anti-angiogenic therapy; (2) in combination with Yervoy (ipilimumab, an anti-CTLA-4 monoclonal antibody) as first-line treatment for patients with intermediate- or high-risk advanced RCC. (Bioon.com)

Original Source: Opdivo® (nivolumab) in Combination with CABOMETYX® (cabozantinib) Demonstrates Significant Survival Benefits in Patients with Advanced Renal Cell Carcinoma in Pivotal Phase 3 CheckMate -9ER Trial