Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Eisai Inc. today announced that the U.S. Food and Drug Administration (FDA) 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 advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. The approval for this population 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 32% (HR=0.68 [95% CI, 0.56-0.84]; p=0.0001), and progression-free survival (PFS), reducing the risk of disease progression or death by 40% (HR=0.60 [95% CI, 0.50-0.72]; p<0.0001), versus chemotherapy (investigator’s choice of doxorubicin or paclitaxel). Keytruda plus Lenvima also demonstrated a statistically significant improvement in objective response rate (ORR), with an ORR of 30% (95% CI, 26-36) versus 15% (95% CI, 12-19) for patients who received investigator’s choice of doxorubicin or paclitaxel, in addition to a complete response rate of 5% for Keytruda plus Lenvima versus 3% for doxorubicin or paclitaxel and a partial response rate of 25% versus 13%, respectively.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda. Based on the severity of the adverse reaction, Keytruda should be withheld or permanently discontinued and corticosteroids administered if appropriate. Keytruda can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, Keytruda can cause fetal harm when administered to a pregnant woman. For more information, see “Selected Important Safety Information” below.

Adverse reactions, some of which can be serious or fatal, may occur with Lenvima, including hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure or impairment, proteinuria, diarrhea, fistula formation and gastrointestinal perforation, QT interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, impairment of thyroid stimulating hormone suppression/thyroid dysfunction, impaired wound healing and osteonecrosis of the jaw. Based on the type and/or severity of the adverse reaction, Lenvima may be interrupted, reduced and/or discontinued. Based on its mechanism of action and data from animal reproduction studies, Lenvima can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should be advised to use effective contraception. For more information, see “Selected Safety Information” below.

“With a five-year survival rate of just 17%, women with advanced endometrial cancer who are not candidates for curative therapy, particularly those with disease progression following prior systemic therapy, have limited treatment options,” said Dr. Vicky Makker, principal investigator and medical oncologist, Memorial Sloan Kettering Cancer Center. “This approval is an important step forward in helping patients fight this difficult-to-treat malignancy, as physicians can now provide an option that may improve survival outcomes.”

“When compared to the chemotherapies used in this trial, this combination treatment regimen was proven to extend the lives of certain patients diagnosed with previously treated, advanced endometrial cancer,” said Dr. Gregory Lubiniecki, Vice President, Oncology Clinical Research, Merck Research Laboratories. “Based on Phase 3 data, today’s approval acts as the confirmatory trial to our previous accelerated approval of Keytruda plus Lenvima in patients with certain types of advanced endometrial cancer and reinforces the impact of our joint research with Eisai in exploring the potential of this combination to treat more patients with challenging types of cancer.”

“This FDA approval of Keytruda plus Lenvima for the treatment of patients with certain types of advanced endometrial cancer is an important step forward towards helping this patient community that has had limited treatment options,” said Dr. Takashi Owa, Chief Medicine Creation Officer and Chief Discovery Officer, Oncology Business Group at Eisai. “This marks a culmination of our relentless pursuit to address unmet needs of people with cancer, and we owe our deepest gratitude to those who participated in our KEYNOTE-775/Study 309 trial, their families and clinicians, and to our employees, whose collective commitment made this meaningful milestone possible.”

Keytruda plus Lenvima was previously approved under the FDA’s accelerated approval process, as well as under the agency’s Real-Time Oncology Review pilot program and its Project Orbis initiative, for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation based on data from the KEYNOTE-146/Study 111 trial. In accordance with accelerated approval regulations, continued approval was contingent upon verification and description of clinical benefit; these accelerated approval requirements have been fulfilled with the data from KEYNOTE-775/Study 309.