Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Eisai today announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved the combination of KEYTRUDA, Merck’s anti-PD-1 therapy, plus LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, for the treatment of patients with unresectable, advanced or recurrent endometrial carcinoma that progressed after cancer chemotherapy. This approval marks the first time the combination of KEYTRUDA plus LENVIMA has been approved in Japan. KEYTRUDA plus LENVIMA is now approved in Japan, the U.S. and Europe for certain types of advanced endometrial carcinoma.

“Rates of endometrial carcinoma have been steadily increasing in Japan each year, and there are limited options for patients who are diagnosed at an advanced stage or find their disease has returned,” said Dr. Gregory Lubiniecki, Vice President, Clinical Research, Merck Research Laboratories. “With today’s approval, patients in Japan with unresectable, advanced or recurrent endometrial carcinoma now have the option of the first immunotherapy and tyrosine kinase inhibitor combination that has significantly improved overall survival and progression-free survival compared to chemotherapy.”

“This is the first approval of the KEYTRUDA plus LENVIMA combination in Japan,” said Terushige Iike, President, Eisai Japan at Eisai. “We thank the patients, families and healthcare providers who made this approval possible. By delivering this combination therapy, we are proud to provide patients with advanced or recurrent endometrial carcinoma an additional treatment option.”

The approval is based on results from the pivotal Phase 3 KEYNOTE-775/Study 309 trial, in which KEYTRUDA plus LENVIMA demonstrated statistically significant improvements in overall survival (OS), reducing the risk of death by 38% (HR=0.62 [95% CI, 0.51-0.75]; p<0.0001), and progression-free survival (PFS), reducing the risk of disease progression or death by 44% (HR=0.56 [95% CI, 0.47-0.66]; p<0.0001), versus chemotherapy (investigator’s choice of doxorubicin or paclitaxel). The median OS was 18.3 months (95% CI, 15.2-20.5) for KEYTRUDA plus LENVIMA versus 11.4 months (95% CI, 10.5-12.9) for chemotherapy. The median PFS was 7.2 months (95% CI, 5.7-7.6) for KEYTRUDA plus LENVIMA versus 3.8 months (95% CI, 3.6-4.2) for chemotherapy.

The Japanese package inserts for KEYTRUDA and LENVIMA note that in the KEYNOTE-775/Study 309 trial, adverse reactions were observed in 395 patients (97.3%) out of the safety analysis set of 406 patients (including 51 out of 52 Japanese patients) receiving KEYTRUDA plus LENVIMA. The most common adverse reactions were hypertension in 249 patients (61.3%), hypothyroidism in 222 patients (54.7%), diarrhea in 171 patients (42.1%), nausea in 158 patients (38.9%), decreased appetite in 151 patients (37.2%), fatigue in 113 patients (27.8%), proteinuria in 105 patients (25.9%), vomiting in 98 patients (24.1%), weight decreased in 91 patients (22.4%), arthralgia in 87 patients (21.4%) and palmar-plantar erythrodysesthesia syndrome in 84 patients (20.7%).

Endometrial carcinoma begins in the inner lining of the uterus, which is known as the endometrium, and accounts for more than 90% of uterine cancers. In Japan, it is estimated there were more than 17,000 new cases of uterine cancer and more than 3,000 deaths in 2020 alone. KEYTRUDA and LENVIMA have each received orphan drug designation in Japan for endometrial carcinoma.

In addition to advanced endometrial carcinoma, Merck and Eisai continue to study the KEYTRUDA plus LENVIMA combination across several types of cancer with more than 20 clinical trials.