Merck, Eisai Win FDA Approval for Combination Treatment for Advanced Endometrial Carcinoma

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Merck’s venerable checkpoint inhibitor Keytruda picked up another regulatory approval. On Wednesday, the U.S. Food and Drug Administration (FDA) approved Keytruda in combination with Eisai’s Lenvima for the treatment of patients with advanced endometrial carcinoma.

Keytruda, an anti-PD-1 therapy, and Lenvima, an oral kinase inhibitor, were approved for patients whose carcinoma is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation. The approval of the combination therapy marks the first time the FDA approved a checkpoint inhibitor and a kinase inhibitor for this indication. The combination therapy was approved under the FDA’s accelerated Real-Time Oncology Review pilot program.

Takashi Owa, chief discovery officer and head of medicine creation in Eisai’s oncology business group, noted that at least 75% of endometrial cancer cases are not microsatellite instability-high or mismatch repair deficient. Those patients have been in need of new treatment options for quite some time, Owa said.

“We are excited for the advancement that today’s approval of the Keytruda plus Lenvima combination treatment represents for these women whose advanced endometrial carcinoma is not microsatellite instability-high or mismatch repair deficient, has progressed following prior systemic therapy and who are not candidates for curative surgery or radiation, and we look forward to the possibilities that our collaboration holds,” Owa said in a statement.

The combination therapy was approved based on tumor response rate and durability of response revealed in a mid-stage trial. Data from the Phase II KEYNOTE-146/Study 111 showed that the combination treatment demonstrated a 38.3% objective response rate, with a complete response rate of 10.6% and a partial response rate of 27.7%. In the patients who had a response as determined by independent review at the time of data cutoff, the median duration of response was not reached and 69% of these patients experienced responses lasting six months or greater, the two companies said.

The FDA review of the mid-stage data was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners.

Jonathan Cheng, head of oncology clinical research at Merck Research Laboratories, said the approval of the Keytruda/ Lenvima combination brings the first approved combination treatment to women with this particular type of cancer. Cheng noted that Merck and Eisai are committed to continuing development of the combination treatment through the LEAP (LEnvatinib And Pembrolizumab) clinical program, which is under active investigation

In endometrial carcinoma, the most common adverse reactions for the combination were fatigue, hypertension, musculoskeletal pain, diarrhea, decreased appetite, hypothyroidism, nausea, stomatitis, vomiting, decreased weight, abdominal pain, headache, constipation, urinary tract infection, dysphonia, hemorrhagic events, hypomagnesemia, palmar-plantar erythrodysesthesia, dyspnea, cough and rash.

In addition to advanced endometrial carcinoma, the combination of Keytruda and Lenvima is being investigated for advanced unresectable hepatocellular carcinoma and advanced and/or metastatic renal cell carcinoma. The combination treatment received Breakthrough Therapy Designation from the FDA for each of these indications.

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