The US Food and Drug Administration (FDA) has approved the Promega OncoMate MSI Dx Analysis System as a companion diagnostic to identify patients with microsatellite-stable endometrial carcinoma who could benefit from pembrolizumab (Keytruda) plus lenvatinib (Lenvima).

OncoMate MSI Dx Analysis System is a Polymerase Chain Reaction (PCR)–based assay that evaluates microsatellite stability status in tumour 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.

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

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. Results from the trial were published in January 2022 in the New England Journal of Medicine.

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

The confirmed Objective Response Rate (ORR) was 30.3 percent with the combination regimen vs 15.1 percent with chemotherapy; complete responses were observed in 5.2 percent vs 2.6 percent, 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 three 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 experienced progression after at least one line of platinum-based chemotherapy. Additional enrollment criteria included available biopsy specimens for the determination of MMR status, at least one measurable lesion per RECIST v1.1, and an ECOG performance status of zero or one.

The primary endpoints of the trial were PFS per blinded independent central review per RECIST v1.1 and OS. Secondary endpoints 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 percent of the combination group vs 99.5 percent of the chemotherapy group; grade 3 or higher AEs occurred in 88.9 percent and 72.7 percent.

The most common AEs in the combination group were hypertension (64 percent), hypothyroidism (57.4 percent), and diarrhoea (54.2 percent). Grade 5 AEs were observed in 5.7 percent of the combination group vs 4.9 percent of the chemotherapy group. The most common serious AE in the combination group was hypertension (4.2 percent) vs febrile neutropenia (4.1 percent) in the chemotherapy group.

Additionally, the Quality of Life Questionnaire Core 30 (QLQ-C30) was completed for more than 95 percent 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.