European Commission Approves BMS/Ipsen 'Immuno-Oncology + Targeted Therapy' Combination of Opdivo + Cabometyx for First-Line Treatment of Advanced Renal Cell Carcinoma

March 31, 2021 /BioValleyBIOON/ -- Recently, the European Commission (EC) approved Bristol-Myers Squibb’s (BMS) anti-PD-1 therapy Opdivo (Opdivo, generic name: nivolumab) in combination with Ipsen’s targeted anticancer drug Cabometyx (cabozantinib) for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). This approval is based on data from the pivotal Phase 3 CheckMate-9ER trial. The results showed that, compared to the first-line standard-of-care drug Sutent (Sutent, generic name: sunitinib, a tyrosine kinase inhibitor,PfizerCompared with [the control], the “immunotherapy + targeted therapy” regimen consisting of Opdivo and Cabometyx demonstrated sustained therapeutic benefits and significantly improved quality of life.

Cabometyx is marketed by Exelixis in the U.S. market and by Takeda in the Japanese market. Ipsen has obtained exclusive commercialization rights for Cabometyx in markets outside the United States and Japan.

In terms of U.S. regulatory oversight,FDAIn January 2021, the Opdivo + Cabometyx regimen was approved for first-line treatment of patients with advanced renal cell carcinoma (RCC). The “immunotherapy + targeted therapy” combination of Opdivo and Cabometyx received priority review and real-timeTumorThe Real-Time Oncology Review (RTOR) pilot program has been approved for all International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk categories, providing an important new first-line treatment option for patients with previously untreated advanced or metastatic renal cell carcinoma (RCC).

This approval expands Bristol-Myers Squibb’s position in first-line advanced RCC. Previously, the dual immunotherapy regimen of Opdivo and Yervoy (ipilimumab, an anti-CTLA-4 monoclonal antibody) had been approved as the standard of care for first-line treatment of patients with intermediate- or poor-risk advanced RCC.

Kidney Cancer (Image source: vecteezy.com)

The approval of the Opdivo + Cabometyx regimen was based on the results of the pivotal Phase III CheckMate-9ER trial. The data demonstrated that, in patients with previously untreated advanced renal cell carcinoma (RCC), the “immunotherapy + targeted therapy” combination of Opdivo + Cabometyx showed significant improvements across all efficacy endpoints—including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR)—compared with Sutent (sunitinib, a tyrosine kinase inhibitor developed by Pfizer), the standard first-line care.

Specific data are as follows: (1) For overall survival (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), with median OS not reached in either group. (2) For the primary endpoint, progression-free survival (PFS), the Opdivo + Cabometyx group demonstrated a twofold improvement 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) For objective response rate (ORR), the Opdivo + Cabometyx group achieved twice the rate of the Sutent group (56% vs. 27%), along with a higher complete response (CR) rate (8% vs. 5%). (4) For duration of response (DOR), the Opdivo + Cabometyx group had a longer DOR compared with the Sutent group (median DOR: 20.2 months vs. 11.5 months). Notably, all these key efficacy outcomes were consistent across 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.

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 RCC with the Opdivo and Cabometyx “immunotherapy + targeted therapy” combination regimen yields 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.

The active pharmaceutical ingredient of Cabometyx is cabozantinib, a tyrosine kinase inhibitor (TKI) that exerts its 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) and patients with hepatocellular carcinoma (HCC) who have previously been treated with sorafenib.

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor designed to uniquely harness the body’sAutoimmunitySystem-assisted recovery of anti-TumorImmune Response. Opdivo was first approved in Japan in July 2014, becoming the world’s first approved PD-1 immunotherapy. Currently, Opdivo has become an important treatment option for various types of cancer.

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 poor-risk advanced RCC. (Bioon.com)

Original Source: European Commissionapproves Cabometyx® in Combination With Opdivo® as a First-Line Treatment for Patients Living With Advanced Renal Cell Carcinoma