Approval Announcement
KENILWORTH, N.J., & WOODCLIFF LAKE, N.J.-- September 17, 2019 -- Merck (NYSE: MRK, known as MSD outside the U.S. and Canada) and Eisai announced the U.S. Food and Drug Administration (FDA) has approved the combination of Keytruda (pembrolizumab) (Merck’s anti-PD-1 therapy) plus Lenvima (lenvatinib) (Eisai’s orally available kinase inhibitor) for the treatment of specific patients with advanced endometrial carcinoma.
Key Approval Milestones
This is the first U.S. approval for the Keytruda plus Lenvima combination.
It is also the first time an anti-PD-1 therapy has been approved in combination with a kinase inhibitor for advanced endometrial carcinoma in the U.S.
Approval Process Details
The application was submitted on June 17 and reviewed under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to streamline the review process and make treatments available to patients earlier.
The review was also conducted under Project Orbis (an initiative of the FDA Oncology Center of Excellence), which enables concurrent submission and review of oncology drugs among international partners. Under this project, the FDA, Australian Therapeutic Goods Administration (TGA), and Health Canada collaboratively reviewed the application, allowing for simultaneous decisions in all three countries.
Indicated Patient Population
The combination is approved for patients with advanced endometrial carcinoma who meet all the following criteria:
The cancer is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).
Disease progression has occurred following prior systemic therapy.
Patients are not candidates for curative surgery or radiation.
Approval Basis
The approval is based on tumor response rate and durability of response. Continued approval for this indication may depend on verification and description of clinical benefit in a confirmatory trial.
Expert Commentary
“When diagnosed early, endometrial carcinoma can have a good prognosis; however, for women whose cancer has progressed following prior systemic therapy, there are few FDA-approved treatment options,” said Dr. Vicky Makker, medical oncologist at Memorial Sloan Kettering Cancer Center. “Based on objective response rate and the duration of response, this approval of the Keytruda plus Lenvima combination will help address a significant unmet medical need for 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.”
Safety Profile
The Keytruda plus Lenvima combination carries safety risks associated with each individual agent, requiring careful monitoring and appropriate management.
Keytruda (pembrolizumab)-Associated Safety Risks
Immune-Mediated Adverse Reactions: These reactions may be severe or fatal and can occur in various organ systems, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT).
Management: Based on the severity of the adverse reaction, Keytruda should be withheld or discontinued, and corticosteroids administered if appropriate.
Infusion-Related Reactions: Keytruda can cause severe or life-threatening infusion-related reactions.
Fetal Harm: Based on its mechanism of action, Keytruda can cause fetal harm when administered to pregnant women.
Lenvima (lenvatinib)-Associated Safety Risks
Adverse reactions associated with Lenvima (some of which may be severe or fatal) include:
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
Wound healing complications
Management: Based on the type and/or severity of the adverse reaction, Lenvima may be interrupted, reduced, and/or discontinued.
Fetal Harm: Based on its mechanism of action and animal reproduction studies, Lenvima can cause fetal harm. Females of reproductive potential should be advised to use effective contraception.
