FDA Grants Breakthrough Therapy Status to Lenvima-Keytruda Combo for Advanced Liver Cancer

The U.S. Food and Drug Administration (FDA) has granted the designation of breakthrough therapy to Keytruda (pembrolizumab) in combination with Lenvima (lenvatinib) as a first-line treatment for patients with advanced unresectable hepatocellular carcinoma (HCC) that is not suitable for localized treatment.

The designation of breakthrough therapy is given to medications that provide significant advantages over currently available options. It is intended to accelerate the development, review, and approval of medications to treat serious or life-threatening conditions.

Keytruda is an anti-PD-1 checkpoint blockade immunotherapy developed by Merck (known as MSD outside the U.S. and Canada) that has been approved by the FDA and by the European Medicines Agency (EMA) for the treatment of several types of cancer.

Lenvima is an oral kinase inhibitor, developed by Eisai, that has been approved for the treatment of patients with advanced renal cell carcinoma. Kinases are specific enzymes found in cells that are involved in blood vessel formation, and tumor growth and progression — processes that the treatment is meant to prevent.

The Lenvima-Keytruda combo therapy received the designation of breakthrough therapy in January 2018 for the treatment of patients with advanced forms of kidney cancer and in July 2018 for endometrial carcinoma.

The FDA’s decision to grant this designation for HCC was based on the latest findings from the Phase 1b KEYNOTE-524/Study 116 (NCT03006926), which were recently presented at the American Association for Cancer Research Annual Meeting 2019.

The multi-center, open-label, single-arm study was designed to assess the safety and efficacy of the Lenvima-Keytruda combo in patients with advanced HCC. All participants were treated with Keytruda administered intravenously at a dose of 200 mg every three weeks, in combination with Lenvima administered orally at a daily dose of 8 mg or 12 mg, depending on the patient’s body weight.

The trial is divided into two parts: an initial phase to determine the safety and tolerability of the combination therapy, and a second expansion phase to examine the patients’ objective responses and duration of responses to the therapy.

The safety and tolerability of the combo therapy has been confirmed during the first part of the trial. Analysis of the patients’ responses to treatment is now underway.

“As part of our ongoing collaboration with Eisai, we are committed to evaluating the potential of Keytruda plus Lenvima across a number of different types of cancer,” Jonathan Cheng, MD, vice president of oncology clinical research at Merck Research Laboratories, said in a press release.

“With this breakthrough therapy designation from the FDA, we look forward to working with Eisai to potentially build upon our existing indications for this difficult-to-treat cancer, so that we can help patients through a combination approach,” Cheng added.

Added Takashi Owa, a vice president at Eisai: “We are excited that the FDA has recognized the potential of Keytruda plus Lenvima in combination in advanced unresectable hepatocellular carcinoma not amenable to locoregional treatment with this breakthrough therapy designation. We are dedicated to working together with Merck to potentially bring another important option to patients.”