FDA Approves Opdivo (nivolumab) Plus Cabometyx (cabozantinib) as First-Line Immunotherapy-Targeted Combination for Advanced Renal Cell Carcinoma, Demonstrating Superior Efficacy Over Sutent

January 26, 2021/BioonBIOON/-- Bristol-Myers Squibb (BMS) and its partner Exelixis, Inc. recently announced that the U.S. Food and Drug Administration (FDA) has approved the anti-PD-1 therapy Opdivo (nivolumab) in combination with the targeted anticancer drug Cabometyx (cabozantinib) for the first-line treatment of patients with advanced renal cell carcinoma (RCC). For administration, Opdivo is given as an intravenous infusion at a dose of 240 mg every two weeks or 480 mg every four weeks, while Cabometyx is administered orally as a 40 mg tablet once daily.

Opdivo and Cabometyx “Immune + Targeted” Combination Passes Priority Review Program 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.

Bristol-Myers SquibbTumor、ImmunologyAdam Lenkowsky, General Manager of Cardiovascular Disease in the United States, stated: “At Bristol-Myers Squibb, we are dedicated to developing transformative medicines that improve survival for cancer patients. The role of Opdivo plus Yervoy in the first-line treatment of patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC) has been well established. Today’s achievement extends the potential of Opdivo-based combination therapies to a broader patient population. The combination of Opdivo and Cabometyx brings together the strong legacies of these two agents, offering physicians a new combination treatment option for advanced RCC and improving outcomes for patients eligible for this immunotherapy plus tyrosine kinase inhibitor regimen.”

This approval is based on the results of the pivotal Phase III CheckMate-9ER trial. The data show that in patients with previously untreated advanced RCC,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).

Specific data are as follows: (1) For 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 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 ORR, the rate in the Opdivo + Cabometyx group was twice that of the Sutent group (56% vs. 27%), with a higher complete response (CR) rate (8% vs. 5%). (4) For DOR, the Opdivo + Cabometyx group had a longer duration compared with the Sutent group (median DOR: 20.2 months vs. 11.5 months). Notably, all these key efficacy results 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 (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 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 received sorafenib treatment.

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor designed to uniquely harness the human body by blocking the interaction between PD-1 and its ligandsAutoimmunitySystem helps restore resistanceTumorImmune 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 cancers.

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: U.S. Food and Drug Administrationapproves OPDIVO® (nivolumab) in Combination with CABOMETYX® (cabozantinib) as First-line Treatment for Patients with Advanced Renal Cell Carcinoma