MSD and Eisai Announce FDA Approval of KEYTRUDA (pembrolizumab) plus LENVIMA (lenvatinib) Combination for Advanced Endometrial Carcinoma

Today, Merck Sharp & Dohme (MSD) and Eisai jointly announced that the U.S. Food and Drug Administration (FDA) has approved MSD’s blockbuster PD-1 inhibitor Keytruda in combination with the oral tyrosine kinase inhibitor Lenvima for the treatment of patients with specific advanced endometrial cancer. These patients do not have microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors. Their disease progressed following prior systemic therapy, and they are not candidates for curative surgery or radiation. This marks the first approval in the United States for the Keytruda and Lenvima combination.

Notably, this accelerated approval was granted under the FDA’s Real-Time Oncology Review (RTOR) pilot program. Furthermore, under another pilot project by the FDA’s Oncology Center of Excellence, Orbis, the regulatory authorities in the United States, Australia, and Canada concurrently reviewed the application and approved it simultaneously in all three countries today.

Endometrial cancer typically has a favorable prognosis when diagnosed at an early stage; however, treatment options remain very limited for patients whose disease continues to progress despite systemic therapy. Keytruda is a blockbuster PD-1 inhibitor developed by Merck Sharp & Dohme (MSD). It has been approved for more than 20 indications, including melanoma, non-small cell lung cancer, and liver cancer. Lenvima is a tyrosine kinase inhibitor developed by Eisai. It inhibits the activity of VEGFR1–3 and other protein kinases, including FGFR1–4, KIT, and RET. It has been approved for the treatment of various cancers, such as hepatocellular carcinoma and renal cell carcinoma.

This approval was based on the results of KEYNOTE-146/Study 111, an open-label, single-arm Phase 2 clinical trial. A total of 108 patients with metastatic endometrial cancer were enrolled in the trial. Among these 108 patients, 87% (94 patients) had tumors that were not MSI-H or dMMR. In this cohort of 94 patients, the combination of Keytruda and Lenvima achieved an objective response rate (ORR) of 38.3% (95% CI, 29%–49%), with a complete response rate of 10.6% and a partial response rate of 27.7%. At a median follow-up of 18.7 months, the median duration of response had not been reached. Among patients who achieved a response, 69% had a duration of response exceeding 6 months.

“At least 75% of patients with endometrial cancer do not have MSI-H or dMMR tumors. These patients are in urgent need of new treatment options,” said Dr. Takashi Owa, Vice President and Chief Discovery Officer of the Oncology Business Division at Eisai Co., Ltd. “We are pleased that today’s approval provides a new combination therapy for these patients.”

References:

[1] FDA Approves KEYTRUDA® (pembrolizumab) plus LENVIMA® (lenvatinib) Combination Treatment for Patients with Certain Types of Endometrial Carcinoma. Retrieved September 17, 2019, from https://www.businesswire.com/news/home/20190917006151/en/FDA-Approves-KEYTRUDA%C2%AE-pembrolizumab-LENVIMA%C2%AE-lenvatinib-Combination

▽Follow [WuXi AppTecMerck】WeChat Official Account