FDA Clears New CDx for Pembrolizumab/Lenvatinib in Endometrial Carcinoma

The FDA has approved the OncoMate MSI Dx Analysis System as a companion diagnostic for pembrolizumab (Keytruda) plus lenvatinib (Lenvima) in microsatellite-stable (MSS), defined as not microsatellite instability-high (MSI-H), endometrial carcinoma, a key step toward precision treatment strategies.¹

Using a fluorescent, multiplex polymerase chain reaction–based mechanism, the test is designed to identify patients who may benefit from treatment with the combination therapy by analyzing MSI status in tumor tissue.² It requires a 1-ng input of DNA isolated from blood and tumor samples.

With this minimal DNA requirement, a turnaround time ranging from 10 hours to overnight, and high sensitivity and specificity (positive percent agreement, 99.0%; negative percent agreement, 91.7%), the approval offers a new, convenient, and validated tool that can inform clinical decisions rooted in personalized molecular insights for each patient.

“This approval underscores the critical role diagnostics play in accurately matching the right patients, at the right time with the right therapy,” Alok Sharma, director, global clinical market at Promega, said in a news release.¹ “We are committed to delivering reliable tools that guide clinical decisions and help improve patient outcomes.”

Previously, the FDA approved the OncoMate MSI Dx Analysis System as a diagnostic aid for Lynch syndrome in patients with colorectal cancer.¹

Key Clinical Data: KEYNOTE-775

Following an accelerated approval in September 2019, the FDA fully approved the combination of pembrolizumab and lenvatinib in July 2021 for treatment of patients with advanced endometrial carcinoma that is not MSI-H or mismatch repair deficient and has progressed following prior systemic therapy, supported by positive results of the pivotal phase 3 KEYNOTE-775/Study 309 trial (NCT03517449).³

The KEYNOTE-775 trial was a randomized, open-label, multicenter trial that aimed to evaluate the efficacy of the combination therapy vs chemotherapy in advanced endometrial cancer.⁴ The study assessed co–primary end points of progression-free survival (PFS) and overall survival (OS); secondary end points included objective response rate (ORR), health-related quality of life, safety, and pharmacokinetics.

The study enrolled 827 adult patients who were previously treated with at least 1 prior platinum-based chemotherapy regimen in any setting. Patients were randomly assigned 1:1 to receive either pembrolizumab plus lenvatinib or physician’s choice of chemotherapy (doxorubicin or paclitaxel). The investigational regimen entailed 200 mg of pembrolizumab administered by intravenous infusion on day 1 of each 21-day cycle plus 20 mg of oral lenvatinib once daily during each cycle.

The FDA approval was based on the combination therapy arm’s significantly prolonged median PFS (6.6 vs 3.8 months; HR, 0.60; 95% CI, 0.50-0.72; P <.0001) and median OS (17.4 vs 12.0 months; HR, 0.68; 95% CI, 0.56-0.84; P =.0001) compared with chemotherapy.⁵ In addition, the combination yielded a 30% ORR (95% CI, 26%-36%) with a median duration of response (DOR) of 9.2 months, a near doubling of the 15% ORR (95% CI, 12%-19%) and 5.7-month DOR observed in patients who received chemotherapy.

At the time of approval, common treatment-emergent adverse events reported with the combination included hypertension (64.0%), hypothyroidism (57.4%), diarrhea (54.2%), nausea (49.5%), and decreased appetite (44.8%).

Updated efficacy and safety results published in the Journal of Clinical Oncology in 2023 later revealed continued OS, PFS, and ORR benefits by the combination across all subgroups by histology, prior lines of therapy, and MMR status, with no new safety signals observed.⁶

REFERENCES

1. FDA approves Promega OncoMate MSI Dx Analysis System as companion diagnostic for Keytruda in combination with Lenvima in advanced endometrial carcinoma. News release. Promega. November 11, 2025. Accessed November 12, 2025. https://tinyurl.com/bdhyrj5d

2. OncoMate MSI Dx Analysis System. Promega. 2018. Accessed November 12, 2025. https://tinyurl.com/5dufct85

3. FDA grants regular approval to pembrolizumab and lenvatinib for advanced endometrial carcinoma. FDA. Updated February 1, 2022. Accessed November 12, 2025. https://tinyurl.com/5a8ykwh3

4. Lenvatinib in combination with pembrolizumab versus treatment of physician's choice in participants with advanced endometrial cancer (MK-3475-775/E7080-G000-309 per Merck standard convention [KEYNOTE-775]). ClinicalTrials.gov. Updated June 15, 2025. Accessed November 12, 2025. https://www.clinicaltrials.gov/study/NCT03517449

5. Makker V, Colombo N, Herráez AC, et al. Lenvatinib plus pembrolizumab for advanced endometrial cancer. N Eng J Med. 2022;386(5):437-448. doi:10.1056/nejmoa2108330

6. Makker V, Colombo N, Herráez AC, et al. Lenvatinib plus pembrolizumab in previously treated advanced endometrial cancer: updated efficacy and safety from the randomized phase III study 309/KEYNOTE-775. J Clin Oncol. 2023;41(16):2904-2910. doi:10.1200/jco.22.02152