FDA Approves Diagnostic Tool for Pembrolizumab Combo in Endometrial Cancer

The FDA has approved the Promega OncoMate® MSI Dx Analysis System as a companion diagnostic to identify patients with microsatellite stable (MSS) endometrial carcinoma who could benefit from pembrolizumab (Keytruda) plus lenvatinib (Lenvima), according to a press release from the developer, Promega.¹

OncoMate MSI Dx Analysis System is a polymerase chain reaction (PCR)–based assay that evaluates MSI status in tumor tissue. This approval was supported in collaboration with Merck, the marketer of pembrolizumab and lenvatinib.

In July 2021, the OncoMate MSI Dx Analysis System was approved by the FDA as the first PCR-based molecular diagnostic for identifying patients with colorectal cancer who may benefit from additional testing to diagnose Lynch syndrome.²

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

The pembrolizumab plus lenvatinib regimen that the Promega OncoMate MSI Dx Analysis System helps identify patients for was evaluated in the phase 3 KEYNOTE-775 trial (NCT03517449). Based on results from KEYNOTE-775, the regimen was approved by the FDA on July 21, 2021.³ Results from the trial were published in January 2022 in The New England Journal of Medicine.⁴

In patients with advanced mismatch repair-proficient (pMMR) endometrial cancer who received at least 1 platinum-based chemotherapy regimen, the median progression-free survival (PFS) was 6.6 months (95% CI, 5.6-7.4) with pembrolizumab plus lenvatinib compared with 3.8 months (95% CI, 3.6-5.0) with chemotherapy (HR, 0.60; 95% CI, 0.50-0.72; P <.001). The median overall survival (OS) was 17.4 months (95% CI, 14.2-19.9) vs 12.0 months (95% CI, 10.8-13.3), respectively (HR, 0.68; 95% CI, 0.56-0.84; P <.001).

The confirmed objective response rate (ORR) was 30.3% with the combination regimen vs 15.1% with chemotherapy; complete responses were observed in 5.2% vs 2.6%, respectively. The median duration of response was 9.2 months (range, 1.6-23.7) vs 5.7 months (range, 0.0-24.2).

A total of 697 patients were included in the pMMR population, of whom 346 were assigned to receive 200 mg of intravenous pembrolizumab via 30-minute infusion every 3 weeks plus 20 mg of oral lenvatinib once daily, and 351 were assigned to receive chemotherapy.

Eligible patients were 18 years or older with confirmed advanced, recurrent, or metastatic endometrial cancer of any histologic subtype except carcinosarcoma and sarcoma who progressed after at least 1 line of platinum-based chemotherapy. Additional enrollment criteria included available biopsy specimens for the determination of MMR status, at least 1 measurable lesion per RECIST v1.1, and an ECOG performance status of 0 or 1.

The primary end points of the trial were PFS per blinded independent central review per RECIST v1.1 and OS. Secondary end points included ORR, safety, and health-related quality of life.

Regarding safety, the median duration of treatment was 231 days (range, 1-817) for all patients treated with the combination vs 104.5 days (range, 1-785) with chemotherapy. Any adverse event (AE) was experienced by 99.8% of the combination group vs 99.5% of the chemotherapy group; grade 3 or higher AEs occurred in 88.9% and 72.7%.

The most common AEs in the combination group were hypertension (64.0%), hypothyroidism (57.4%), and diarrhea (54.2%). Grade 5 AEs were observed in 5.7% of the combination group vs 4.9% of the chemotherapy group. The most common serious AE in the combination group was hypertension (4.2%) vs febrile neutropenia (4.1%) in the chemotherapy group.

Additionally, the QLQ-C30 was completed for more than 95% of patients in both treatment groups. No substantial differences were observed in the QLQ-C30 global health status quality-of-life scores over time between the groups.

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/2jdnn7r7
2. FDA clears Promega OncoMate® MSI Dx Analysis System. News release. Promega. July 28, 2021. Accessed November 12, 2025. https://tinyurl.com/5n8hhwey
3. FDA grants regular approval to pembrolizumab and lenvatinib for advanced endometrial carcinoma. News release. FDA. July 21, 2021. Accessed November 12, 2025. https://tinyurl.com/49hzfsvh
4. Makker V, Colombo N, Casado Herráez A, et al. Lenvatinib plus pembrolizumab for advanced endometrial cancer. N Engl J Med. 2022;386(5):437-448. doi:10.1056/NEJMoa2108330