The FDA approved pembrolizumab plus lenvatinib combination therapy for the first-line treatment of a

Merck & Co., Inc. and Eisai Co., Ltd. jointly announced today that the U.S. Food and Drug Administration (FDA) has approved Merck’s anti-PD-1 therapy pembrolizumab in combination with Eisai’s investigational oral multi-receptor tyrosine kinase inhibitor lenvatinib for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

This approval is based on the results of the pivotal Phase 3 clinical trial CLEAR (Study 307)/KEYNOTE-581. In this trial, compared with sunitinib, the combination of pembrolizumab and lenvatinib demonstrated statistically significant improvements across key efficacy endpoints, including progression-free survival (PFS), overall survival (OS), and confirmed objective response rate (ORR).

In terms of progression-free survival, the combination of pembrolizumab and lenvatinib reduced the risk of disease progression or death by 61% (hazard ratio [HR] = 0.39 [95% confidence interval (CI): 0.32–0.49]; p<0.0001), with a median PFS of 23.9 months versus 9.2 months in the sunitinib group. For overall survival, the combination lowered the risk of death by 34% (HR = 0.66 [95% CI: 0.49–0.88]; p=0.0049). Additionally, the confirmed objective response rate was 71% (95% CI: 66–76) among patients treated with the pembrolizumab-lenvatinib combination (n=252), compared with 36% (95% CI: 31–41) in the sunitinib group (n=129). The pembrolizumab-lenvatinib group achieved a complete response (CR) rate of 16% and a partial response (PR) rate of 55%, whereas the sunitinib group had CR and PR rates of 4% and 32%, respectively.

Immune-mediated adverse reactions can occur in any organ system or tissue, may affect multiple body systems simultaneously, and can be severe or fatal. Such reactions can occur at any time during or after pembrolizumab treatment, including pneumonitis, colitis, hepatitis, endocrine disorders, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Early identification and management of immune-mediated adverse reactions are critical to ensuring the safe use of pembrolizumab. Depending on the severity of the adverse reaction, pembrolizumab should be withheld or permanently discontinued, and corticosteroid therapy should be administered as appropriate. Pembrolizumab may also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, pembrolizumab can cause fetal harm when administered to pregnant women.