FDA Approves Companion Diagnostic for Pembrolizumab in MSI-H Solid Tumors

The FDA has approved the OncoMate MSI Dx Analysis System as a companion diagnostic to identify patients with microsatellite instability–high (MSI-H) solid tumors who may be eligible for treatment with pembrolizumab (Keytruda).¹

In March 2023, the FDA granted full approval to pembrolizumab for the treatment of adult and pediatric patients with unresectable or metastatic MSI-H or mismatch repair–deficient (dMMR) solid tumors that have progressed following previous treatment and who have no satisfactory alternative options.²

The full approval was supported by pooled data in patients with more than 30 cancer types enrolled across 3 multicenter, nonrandomized, open-label, multicohort phase 2 trials: KEYNOTE-164 (NCT02460198), KEYNOTE-158 (NCT02628067), and KEYNOTE-051 (NCT02332668). At a median follow-up of 20.1 months (range, 0.1-71.4), pembrolizumab (n = 504) produced a pooled objective response rate (ORR) of 33.3% (95% CI, 29.2%-37.6%), including a complete response rate of 10.3% and a partial response rate of 23.0%. The median duration of response (DOR) was 63.2 months (range, 1.9+ to 63.9+).

“This [companion diagnostic] approval reflects our dedication to providing meaningful diagnostic advances, developed to the highest quality and regulatory standards,” Alok Sharma, Global Clinical Market director at Promega, stated in a news release.¹ “Our test connects patients with the therapy most likely to help them, working alongside our pharmaceutical collaborators and the clinicians who use the result.”

What does the OncoMate MSI Dx Analysis System detect?

The OncoMate MSI Dx Analysis System, developed by Promega Corporation in collaboration with Merck, is a polymerase chain reaction (PCR)–based assay that evaluates MSI status in solid tumor tissue.¹

The assay was previously cleared by the FDA as the first PCR-based molecular diagnostic to identify patients with colorectal cancer (CRC) who may benefit from additional testing for Lynch syndrome. It was also approved as a companion diagnostic to identify patients with microsatellite-stable endometrial carcinoma who may benefit from pembrolizumab plus lenvatinib (Lenvima). Outside the United States, the system carries CE marking under the European Union In Vitro Diagnostic Regulation and is approved by China's National Medical Products Administration as a companion diagnostic for pembrolizumab in MSI-H solid tumors.

What data supported the full approval of pembrolizumab in MSI-H/dMMR solid tumors?

KEYNOTE-164 enrolled 124 patients with MSI-H or dMMR CRC whose disease had progressed following treatment with a fluoropyrimidine plus oxaliplatin or irinotecan.² KEYNOTE-158 included 373 patients with MSI-H or dMMR non-CRC solid tumors, with cohort K enrolled prospectively, and cohorts A through J identified retrospectively. KEYNOTE-051 featured 7 pediatric patients with MSI-H or dMMR cancers.

Adult patients received pembrolizumab at 200 mg intravenously every 3 weeks, and pediatric patients received 2 mg/kg intravenously every 3 weeks, until unacceptable toxicity, disease progression, or a maximum of 24 months of treatment. Response was assessed by blinded independent central review per RECIST 1.1 criteria (modified in KEYNOTE-158) and by investigator assessment in KEYNOTE-051.

Among responders (n = 168), 77% had responses lasting at least 12 months, and 39% had responses lasting at least 36 months. In the CRC cohort (n = 124), the ORR was 34% (95% CI, 26%-43%), with DOR ranging from 4.4 to 58.5+ months. In patients with non-CRC tumors (n = 380), the ORR was 33% (95% CI, 28%-38%), with DOR ranging from 1.9+ to 63.9+ months.

The full approval converted the FDA's May 2017 accelerated approval of pembrolizumab in this setting, which was the agency's first tissue- and site-agnostic indication; the 2017 decision was based on an ORR of 39.6% (95% CI, 31.7%-47.9%) among patients enrolled (n = 149) across 5 single-arm trials.³

What is the safety profile of pembrolizumab in this population?

Median exposure to pembrolizumab was 6.2 months (range, 1 day to 53.5 months) in KEYNOTE-158 and KEYNOTE-164 and 2.1 months (range, 1 day to 25 months) in KEYNOTE-051.² Adverse effects in patients with MSI-H or dMMR cancers were similar to those observed in patients with other solid tumors who received single-agent pembrolizumab.

Among 2,799 patients who received single-agent pembrolizumab across the label safety population, immune-mediated pneumonitis occurred in 3.4% of patients, including grade 3 events in 0.9%, grade 4 events in 0.3%, and fatal events in 0.1%. Immune-mediated colitis occurred in 1.7% of patients (grade 3, 1.1%; grade 4, <0.1%), immune-mediated hepatitis in 0.7% (grade 3, 0.4%), and infusion-related reactions in 0.2%.

References

1. FDA approves Promega OncoMate MSI Dx Analysis System as companion diagnostic for Keytruda in MSI-high solid tumors. News release. Promega Corporation. November 10, 2026. Accessed November 10, 2026. https://www.businesswire.com/news/home/20261109651021/en/FDA-Approves-Promega-OncoMate-MSI-Dx-Analysis-System-as-Companion-Diagnostic-for-KEYTRUDA-in-MSI-High-Solid-Tumors
2. FDA converts to full approval indication for Keytruda (pembrolizumab) for certain adult and pediatric patients with advanced microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors. News release. Merck. March 29, 2023. Accessed November 10, 2026. https://www.merck.com/news/fda-converts-to-full-approval-indication-for-keytruda-pembrolizumab-for-certain-adult-and-pediatric-patients-with-advanced-microsatellite-instability-high-msi-h-or-mismatch-repair-deficient/
3. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. FDA. May 23, 2017. Accessed November 10, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-first-tissuesite-agnostic-indication