FDA Approves LENVIMA plus KEYTRUDA Combination Therapy for Advanced Endometrial Cancer in Patients with Non-MSI-H or pMMR Tumors

Tokyo and Kenilworth, New JerseyOctober 17, 2019 /PRNewswire/ -- Eisai (CEO: Haruo Naito) and Merck (NYSE: MRK), Kenilworth, New Jersey, U.S.A., today announced that the U.S. Food and Drug Administration (FDA) has approved the combination therapy of LENVIMA (an oral kinase inhibitor discovered by Eisai) and KEYTRUDA (an anti-PD-1 therapy from Merck, Kenilworth, New Jersey, U.S.A.) for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have experienced disease progression following prior systemic therapy and are not candidates for curative surgery or radiation. This marks the first approval in the United States of the LENVIMA plus KEYTRUDA combination regimen, as well as the first approval in the United States of an anti-PD-1 therapy combined with a kinase inhibitor for the treatment of advanced endometrial carcinoma. Following the submission of the application on June 17, this approval underwent accelerated review under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to improve the efficiency of the application review process to ensure patients receive treatment as early as possible. The RTOR allows the FDA to review most of the data in advance before the applicant formally submits a complete application. This accelerated approval was based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. According to the FDA, this review was conducted under the Orbis Project initiated by the FDA Oncology Center of Excellence.

The Orbis Project provides a framework for the concurrent submission and review of oncology drugs among its international partners. Under this initiative, the U.S. Food and Drug Administration (FDA), the Australian Therapeutic Goods Administration (TGA), and Health Canada jointly reviewed applications for two oncology drugs, enabling simultaneous regulatory decisions in all three countries.

This approval is based on data from Study 111/KEYNOTE-146, a Phase 2, multi-cohort, multicenter, open-label, single-arm trial that enrolled 108 patients with metastatic endometrial cancer who had experienced disease progression after at least one prior systemic therapy in any setting. Among the 94 patients whose tumors were not MSI-H or dMMR, the combination therapy of LENVIMA + KEYTRUDA demonstrated an objective response rate (ORR) of 38.3% (95% CI, 29–49), with a complete response rate of 10.6% (n=10) and a partial response rate of 27.7% (n=26). Among patients who responded as determined by independent review (n=36), the median duration of response (DOR) was not reached at the time of data cutoff (range: 1.2+ to 33.1+ months); of these, 69% had responses lasting 6 months or longer. The most common adverse reactions associated with the combination therapy of LENVIMA + KEYTRUDA included (>=20%) were fatigue, musculoskeletal pain, hypertension, diarrhea, decreased appetite, hypothyroidism, nausea, stomatitis, vomiting, weight loss, abdominal pain, headache, constipation, urinary tract infection, dysphonia, hemorrhagic events, hypomagnesemia, hand-foot syndrome, dyspnea, cough, and rash.

“Endometrial cancer can have a favorable prognosis when diagnosed early; however, there are few FDA-approved treatment options for women whose cancer has progressed after prior systemic therapy,” said Dr. Vicky Makker, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. “Based on objective response rate and duration of response, the approval of the LENIVIMA + KEYTRUDA combination regimen will help address the significant unmet medical need in patients with advanced endometrial cancer who are non-MSI-H or dMMR, have experienced disease progression after prior systemic therapy, and are not candidates for curative surgery or radiation.”

Dr. Jonathan Cheng, Vice President of Oncology Clinical Research at MSD, stated, “Today’s approval of the LENVIMA + KEYTRUDA combination therapy for the treatment of advanced endometrial cancer with disease progression following prior systemic therapy provides the first approved combination regimen for women with such cancers whose tumors are not MSI-H or dMMR and who are not candidates for curative surgery or radiation therapy, demonstrating the potential of our collaboration with Eisai.”。”。

“MSD is committed to developing this combination therapy through the LEAP (Lenvatinib and Pembrolizumab) clinical program, which is currently under active investigation.”

Dr. Takashi Owa, Vice President of Eisai’s Oncology Business Group and Chief Drug Creation and Chief Discovery Officer, stated, “At least 75% of endometrial cancer cases are not of the high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR) type, and these women have long been in need of new treatment options.” “We are delighted to have been selected for the Real-Time Oncology Review (RTOR) pilot program launched by the FDA last year, and to have received approval for the combination therapy of LENVIMA plus KEYTRUDA approximately three months after submission. This approval is for the treatment of adult patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have experienced disease progression following prior systemic therapy and are not candidates for curative surgery or radiation therapy. We look forward to providing this combination therapy to women with specific types of advanced endometrial cancer.”