The FDA has granted a breakthrough therapy designation for Eisai’s multiple receptor tyrosine kinase inhibitor lenvatinib mesylate (Lenvima) in combination with Merck’s anti-programmed death-1 therapy pembrolizumab (Keytruda) for the potential treatment of patients with advanced and/or metastatic renal cell carcinoma.
Eisai and Merck are jointly developing the combination therapy. This is the second breakthrough therapy designation for lenvatinib and the 12th granted to pembrolizumab.
This designation was based on the results of the renal cell carcinoma cohort in Study 111, a multicenter, open-label, phase 1b/2 clinical study being carried out in the United States and the European Union to evaluate the efficacy and safety of the two drugs in combination in patients with selected solid tumors.
The primary objective of the phase 1b part of Study 111 was to determine the maximum tolerated dose. Patients with unresectable solid tumors (renal cell carcinoma, endometrial cancer, non–small-cell lung cancer, urothelial cancer, squamous cell, head and neck cancer, and melanoma) who had progressed after treatment with approved therapies or for which there are no standard effective therapies available were administered 24 mg of lenvatinib orally daily and 200 mg of pembrolizumab intravenously every three weeks. Dose reductions of lenvatinib were permitted based on observed toxicity.
The phase 2 part of Study 111 was conducted in patients who had select solid tumors with zero to two prior lines of systemic therapy (unless discussed with the sponsor) with a recommended dosage of 20 mg of lenvatinib daily and 200 mg of pembrolizumab every three weeks as determined based on the results of the phase 1b portion of the study. The primary endpoint of phase 2 was objective response rate at 24 weeks after treatment began, with select secondary endpoints, including 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.
Source: Eisai, January 9, 2018.