FDA Grants Breakthrough Designation to Lenvima/Keytruda Combination

The FDA this week granted a third Breakthrough Therapy designation to lenvatinib (Lenvima), an oral kinase inhibitor used in combination with the anti-PD-1 therapy pembrolizumab (Keytruda).

The most recent designation is for the treatment of patients with advanced and/or metastatic non-microsatellite instability high/proficient mismatch repair endometrial carcinoma (EC) who progressed following at least 1 prior systemic therapy, according to a press release. The combination therapy is being developed through a collaboration between Eisai and Merck, which was announced in March 2018. Most recently, the lenvatinib/pembrolizumab combination was granted breakthrough designation for the treatment of advanced and/or metastatic renal cell carcinoma in January 2018.

“This second Breakthrough Therapy designation for the Lenvima/Keytruda combination represents another step forward in our collaboration with Eisai and supports the continued evaluation of this combination in more than 11 types of cancer,” Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said in a press release. “We will continue to work closely with Eisai to build on the robust data for the Lenvima/Keytruda combination in advanced endometrial carcinoma in an effort to offer a new option for these patients and potentially help address a critical unmet need.”

The designation followed interim results from Study 111/KEYNOTE-146, a multicenter, open-label, single-arm phase 1b/2 basket trial examining the safety and efficacy of the combination in patients with selected solid tumors. In the trial, the researchers are administering lenvatinib at 20 mg/day with pembrolizumab at 200 mg intravenously every 3 weeks in patients with renal cell carcinoma, EC, non-small cell lung cancer, urothelial cancer, squamous cell head and neck cancer, and melanoma.

The primary endpoint for phase 1b of the study is to evaluate the maximum-tolerated dose of the combination, while the primary endpoint of the ongoing phase 2 portion is investigator-assessed objective response rate at week 24 based on immune-related Response Evaluation Criteria In Solid Tumors, according to the press release.

“We designed Study 111 to learn as much as we could about the Lenvima/Keytruda combination as efficiently as possible, driven by a sense of urgency to bring forward a potential new treatment option for patients in need,” said Dr. Takashi Owa, PhD, vice president and chief medicine creation officer, Oncology Business Group, Eisai. “We are encouraged by the continued activity seen in patients with endometrial carcinoma, and the latest Breakthrough Therapy designation for Lenvima and Keytruda has strengthened our commitment, as part of our human health care mission, to expedite the path to ultimately benefitting patients living with endometrial carcinoma as quickly as possible.”