FDA Grants Regular Approval to Pembrolizumab/Lenvatinib for Advanced Endometrial Carcinoma

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On July 21, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) in combination with lenvatinib (Lenvima) for 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 therapy.

The FDA granted accelerated approval to pembrolizumab with lenvatinib for advanced endometrial carcinoma on September 17, 2019.

KEYNOTE-775/Study 309

KEYNOTE-775/Study 309 ( identifier NCT03517449) was a multicenter, open-label, randomized, active-controlled trial required to confirm the clinical benefit of this accelerated approval.

The study enrolled 827 patients with advanced endometrial carcinoma previously treated with at least one prior platinum-based chemotherapy regimen in any setting, including neoadjuvant and adjuvant treatments. Patients were randomly assigned 1:1 to either pembrolizumab at 200 mg intravenously every 3 weeks with lenvatinib at 20 mg orally once daily or investigator’s choice of doxorubicin or paclitaxel.

The major efficacy outcome measures were progression-free survival (as assessed by blinded independent central review) and overall survival. Additional efficacy outcome measures included objective response rate and duration of response (also assessed by blinded independent central review).

For patients with advanced endometrial cancer that is not MSI-H or dMMR, the median progression-free survival was 6.6 months (95% confidence interval [CI] = 5.6–7.4) for patients in the pembrolizumab and lenvatinib group and 3.8 months (95% CI = 3.6–5.0) for those receiving investigator’s choice chemotherapy (hazard ratio [HR] = 0.60, 95% CI = 0.50–0.72, P < .0001). Median overall survival was 17.4 months (95% CI = 14.2–19.9) and 12.0 months (95% CI = 10.8–13.3), respectively (HR = 0.68, 95% CI = 0.56–0.84, P = .0001). The objective response rate was 30% (95% CI = 26%–36%) and 15% (95% CI = 12%–19%), respectively (P < .0001). Median duration of response was 9.2 months (1.6+, 23.7+) and 5.7 months (0.0+, 24.2+).

The most common adverse reactions reported in ≥ 20% of patients in trials of pembrolizumab in combination with lenvatinib were hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight loss, abdominal pain, urinary tract infection, proteinuria, constipation, headache, hemorrhagic events, palmar-plantar erythrodysesthesia, dysphonia, and rash.

The recommended pembrolizumab dose for endometrial carcinoma is 200 mg every 3 weeks or 400 mg every 6 weeks with lenvatinib at 20 mg orally once daily.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 6 weeks prior to the FDA goal date.

This application was granted Priority Review. The combination of pembrolizumab and lenvatinib received Breakthrough Therapy designation for this indication.


The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.