Lenvatinib, Pembrolizumab Combination Therapy for Patients With RCC Granted Breakthrough Therapy Designation

The FDA has granted Breakthrough Therapy Designation for lenvatinib and pembrolizumab as combination therapy for advanced and/or metastatic renal cell carcinoma (RCC), announced Merck.

Eisai’s multiple receptor tyrosine kinase inhibitor lenvatinib (Lenvima) and Merck’s anti—PD-1 therapy pembrolizumab (Keytruda) as a combination therapy received the designation based on results from the RCC cohort in Study 111. The multi-center, open-label phase 1b/2 clinical study in the United States and European Union evaluated the efficacy and safety of lenvatinib in combination with pembrolizumab in patients with selected solid tumors.

"The FDA's Breakthrough Therapy Designation for the Lenvima and Keytruda combination in advanced and/or metastatic renal cell carcinoma provides us with the opportunity to accelerate our effort to bring an important potential treatment option to these patients," said Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, in a statement.

The primary objective of the phase 1b part of the study was to determine the maximum tolerated dose. Patients with unresectable tumors (RCC, 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 current standard effectice therapies available were included in the study. The participants were administered 24 mg of lenvatinib orally daily in addition to 200 mg of pembrolizumab intravenously every 3 weeks.

Phase 2 of the study was conducted with patients who had select solid tumors with 0 to 2 prior lines of systematic therapy with a recommended dosage of 20 mg of lenvatinib daily in addition to 200 mg of pembrolizumab every 3 weeks as determined based upon results of phase 1b. The primary endpoint of phase 2 was objective response rate at 24 weeks after treatment was initiated, with select secondary endpoints including: objective response rate, disease control rate, progression-free survival, and duration of response. According to Merck, phase 2 is underway and enrollment has expanded for the endometrial cancer cohort.

"We are encouraged that the FDA has recognized the potential of Lenvima plus Keytruda for patients with advanced and/or metastatic RCC with the Breakthrough Therapy Designation,” said Takashi Owa, PhD, vice president, chief medicine creation officer, oncology business group, Eisai, said in a statement. “As a human healthcare company dedicated to giving our first thought to patients, we are committed to working closely with Merck and the FDA to expedite this clinical program with the hope that we may offer another important option for patients in need."

The Breakthrough Therapy Designation is an FDA program that expedites the development and review of drugs for serious or life-threatening conditions. To qualify, there must be preliminary clinical evidence that demonstrates that the drug may provide substantial improvement over current available therapies or at least 1 clinically significant endpoint.