Breakthrough Therapy Lenvima/Keytruda Combo Treats Patients with Advanced Kidney Cancer
Eisai's lenvatinib mesylate (Lenvima), a multiple receptor tyrosine kinase inhibitor, in combination with Merck's pembrolizumab (Keytruda), an anti-programmed death-1 therapy, has been granted the breakthrough therapy designation by the FDA for the treatment of patients with advanced kidney cancer.
This designation marks the second breakthrough therapy designation for lenvatinib and the twelfth for pembrolizumab.
The lenvatinib/pembrolizumab combination has shown promise in the treatment of patients with advanced and/or metastatic renal cell carcinoma.
The FDA's decision was based on the results from the renal cell carcinoma (RCC) cohort of Study 111, a multicenter, open-label, phase 1b/2 clinical study conducted in the United States and the European Union.
Study 111 aims to evaluate the efficacy and safety of the combined therapy in patients with selected solid tumors, with the primary objective of determining the maximum tolerated dose in the phase 1b portion.
Patients with unresectable solid tumors (including renal cell carcinoma, endometrial cancer, non-small-cell lung cancer, urothelial cancer, squamous cell head and neck cancer, and melanoma) who had experienced disease progression after treatment with approved therapies were administered a daily oral dose of 24 mg of lenvatinib and an intravenous dose of 200 mg of pembrolizumab every three weeks.
Based on observed toxicity, dose reductions of lenvatinib were allowed. The phase 2 portion of Study 111 focused on selected patients with solid tumors who had received zero to two prior lines of systemic therapy, with a recommended dosage of 20 mg of lenvatinib daily and 200 mg of pembrolizumab every three weeks, determined based on the phase 1b results.
The primary endpoint of the phase 2 part was the objective response rate at 24 weeks after the start of treatment, along with secondary endpoints such as objective response rate, disease control rate, progression-free survival, and duration of response.
Currently, phase 2 is under way, with enrollment expanded for the endometrial cancer cohort.
