Phase 3 KEYNOTE-775/Study 309 Trial Meets Dual Primary End Points in Advanced Endometrial Cancer


The pivotal phase 3 KEYNOTE-775/Study 309 trial evaluating the investigational use of pembrolizumab (Keytruda) plus lenvatinib (Lenvima) met its dual primary end points of overall and progression-free survival in patients with advanced endometrial cancer.

The pivotal phase 3 KEYNOTE-775/Study 309 trial (NCT03517449), designed to evaluate the investigational use of pembrolizumab (Keytruda) plus lenvatinib (Lenvima), met its dual primary end points of overall survival (OS) and progression-free survival (PFS), as well as its key secondary end point of objective response rate (ORR) in patients with advanced endometrial cancer following at least 1 prior platinum-based regimen, according to Merck and Eisai, the developers of the agents.

Importantly, these positive results were reported in the mismatch repair proficient (pMMR) subgroup and the intent-to-treat (ITT) study population, which includes patients with endometrial carcinoma that is pMMR and patients whose disease is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).

“We are encouraged by the data observed in KEYNOTE-775/Study 309, which represent a possible step forward for patients impacted by advanced endometrial carcinoma and support the results seen in the advanced endometrial cancer cohort of KEYNOTE-146/Study 111,” Takashi Owa, vice president, chief medicine creation officer, and chief discovery officer of the Oncology Business Group at Eisai, said in a press release “As more clinical data from the LEAP (LEnvatinib And Pembrolizumab) program are revealed, we cannot help but be energized by the trajectory of our collaboration with Merck and the benefits we hope to provide to patients together. Most importantly, we are grateful for the trust that the patients and healthcare professionals who participated in this trial have shown us.”

The multicenter, randomized, open-label, phase 3 trial enrolled a total of 827 patients. The total study cohort consisted of 697 patients with tumors that were non-MSI-H or pMMR, and 130 patients with tumors that were MSI-H or dMMR.

The study’s dual primary end points are OS and PFS, as assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors Version (RECIST) v1.1. Key secondary end points include ORR by BICR per RECIST v1.1 and safety/tolerability.

Patients were randomized 1:1 to receive either pembrolizumab at a dose of 200 mg intravenously (IV) every 3 weeks for up to 35 cycles (approximately 2 years) in combination with lenvatinib at a dose of 20 mg orally once daily, or chemotherapy with physician’s choice of either doxorubicin at a 60 mg/m2 dose by IV every 3 weeks for up to a maximum cumulative dose of 500 mg/m2 or paclitaxel at a 80 mg/m2 dose by IV on a 28-day cycle (3 weeks of receiving weekly paclitaxel and 1 week of not receiving paclitaxel).

According to an analysis conducted by an independent data monitoring committee, pembrolizumab plus lenvatinib demonstrated a statistically significant and clinically meaningful improvement in OS, PFS, and ORR versus chemotherapy (treatment of physician’s choice of doxorubicin or paclitaxel).

Regarding safety, the safety profile of combination treatment with pembrolizumab plus lenvatinib was found to be consistent with previously reported studies.

Moving forward, Merck and Eisai intend to discuss these data with regulatory authorities worldwide. The companies also plan to submit marketing authorization applications based on these results and present these results at an upcoming medical meeting.

Of note, KEYNOTE-775/Study 309 is the confirmatory trial for KEYNOTE-146/Study 111, which supported the FDA accelerated approval of the pembrolizumab plus lenvatinib combination in 2019 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. More specifically, this accelerated approval was based on tumor response rate and durability of response and was the first approval granted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among its international partners. Health Canada and Australia’s Therapeutic Goods Administration (TGA) also granted conditional and provisional approvals, respectively, under Project Orbis for this indication.


KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib) Combination Demonstrated Statistically Significant Improvement in Overall Survival, Progression-Free Survival and Objective Response Rate Versus Chemotherapy in Patients With Advanced... [news release]. Kenilworth, NJ & Woodcliff Lake, NJ. Published December 16, 2020. Accessed December 16, 2020.

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