“This approval underscores the critical role diagnostics play in accurately matching the right patients, at the right time with the right therapy,” Alok Sharma, PhD, global clinical market director at Promega shared in a news release. “We are committed to delivering reliable tools that guide clinical decisions and help improve patient outcomes.”
The July 22, 2021, FDA approval of pembrolizumab in combination with lenvatinib represented a significant advancement for patients with advanced endometrial carcinoma that is not microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR).2 This approval was based on data from the phase 3 KEYNOTE-775/Study 309 trial (NCT03517449), which demonstrated meaningful improvements in overall survival (OS) and progression-free survival (PFS) with pembrolizumab/lenvatinib compared with standard chemotherapy.
Findings after 5 years of follow-up confirmed the durability of this survival benefit. In the mismatch repair–proficient subgroup, OS rates were 16.7% with pembrolizumab plus lenvatinib and 7.3% with standard chemotherapy, respectively. The median follow-up for these respective regimens was 68.8 months (range, 60.8-79.0 for combination; range, 60.9-80.0 for chemotherapy). Notably, OS outcomes were consistent with findings observed in the overall study population, in which the combination achieved a 5-year OS rate of 19.9% vs 7.7% with chemotherapy.
“Endometrial carcinoma is difficult-to-treat in the recurrent or advanced stage, especially when tumors are mismatch repair proficient and therefore harder to target with immunotherapy alone,” Vicky Makker, MD, principal investigator of KEYNOTE-775 and a gynecologic medical oncologist at Memorial Sloan Kettering Cancer Center, added. “Five-year follow-up data from the KEYNOTE-775/Study 309 trial show sustained survival benefit in patients treated with pembrolizumab plus lenvatinib and underscore the role of this combination as an effective treatment option for patients with advanced endometrial carcinoma who need further treatment after receiving prior platinum-based therapy.”
What treatment-related adverse effects (TRAEs) were observed with pembrolizumab plus lenvatinib at 5 years of follow-up?
Safety data from KEYNOTE-775/Study 309 showed that pembrolizumab plus lenvatinib continued to be associated with a higher incidence of treatment-related adverse effects than chemotherapy, which is consistent with findings from earlier analyses. TRAEs occurred in 97.3% of patients receiving the combination vs 93.8% of those receiving chemotherapy. Discontinuation of one or both study drugs due to toxicity was more frequent with pembrolizumab plus lenvatinib, occurring in 40.1% of patients (with 16.0% discontinuing both agents). In the chemotherapy arm, the discontinuation rate was 8.0%.
The most commonly reported adverse effects (≥20%) in the combination arm included hypertension (61.8%), hypothyroidism (55.7%), diarrhea (43.3%), nausea (40.1%), decreased appetite (37.9%), fatigue (28.8%), proteinuria (27.6%), vomiting (24.4%), arthralgia (23.9%), decreased weight (22.7%), and palmar-plantar erythrodysesthesia syndrome (20.7%). These findings reinforce the need for proactive monitoring and supportive care strategies when administering pembrolizumab plus lenvatinib, particularly in managing hypertension, thyroid dysfunction, and gastrointestinal toxicities.
What additional regulatory designations has the OncoMate MSI Dx Analysis System received beyond this companion diagnostic clearance?
On July 28, 2021, the FDA cleared the Promega OncoMate™ MSI Dx Analysis System for use in screening for Lynch syndrome in patients with colorectal cancer.1 The test evaluates microsatellite instability (MSI) status, which serves as a key biomarker for identifying individuals who may have an inherited predisposition to cancer associated with Lynch syndrome.
References
- FDA approves Promega OncoMate MSI Dx Analysis System as companion diagnostic for Keytruda in combination with Lenvima in advanced endometrial carcinoma. Promega. News Release. November 11, 2025. Accessed November 11, 2025. https://www.promega.com/aboutus/press-releases/global/2025/november-11-2025-fda-approves-promega-oncomate-msi-dx-analysis-system/
- Keytruda (pembrolizumab) plus Lenvima (lenvatinib) demonstrates durable 5-year survival benefit versus chemotherapy for patients with advanced endometrial carcinoma following one prior platinum-based regimen. Merck. News Release. October 18, 2025. Accessed November 11, 2025. https://www.merck.com/news/keytruda-pembrolizumab-plus-lenvima-lenvatinib-demonstrates-durable-5-year-survival-benefit-versus-chemotherapy-for-patients-with-advanced-endometrial-carcinoma-following-one-prior-pla/
