FDA Approves MSI Companion Diagnostic for Pembrolizumab in MSI-H 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 benefit from pembrolizumab (Keytruda), according to an announcement from the test's developer, Promega.¹

The approval gives laboratories an FDA-approved, PCR-based option for determining MSI status in solid tumor tissue ahead of treatment with the anti–PD-1 agent, which has carried a tumor-agnostic indication for MSI-H or mismatch repair–deficient (dMMR) cancers since 2017.^1,2 The announcement did not include performance data or name a supporting clinical trial.¹

What does the companion diagnostic approval cover?

The test is intended to identify patients with MSI-H solid tumors who may benefit from pembrolizumab, an anti–PD-1 therapy from Merck.¹ Pembrolizumab is indicated for adult and pediatric patients with unresectable or metastatic MSI-H or dMMR cancer that has progressed after prior treatment and who have no satisfactory alternative treatment options.¹ The approval was supported through a collaboration between Promega and Merck.¹

How does the OncoMate MSI Dx test work?

OncoMate MSI Dx is a fluorescent, multiplex PCR-based fragment-sizing assay that evaluates MSI status in solid tumor tissue.^1,3 According to Promega, the system:

• Targets 5 mononucleotide repeat markers (BAT-25, BAT-26, NR-21, NR-24, and MONO-27)⁴
• Uses 2 pentanucleotide markers, Penta C and Penta D, for quality control and sample authentication⁴
• Compares tumor DNA from formalin-fixed, paraffin-embedded (FFPE) tissue with matched normal DNA from FFPE tissue or whole blood⁴
• Runs on the Applied Biosystems 3500 Dx Genetic Analyzer, with results in as little as 10 hours⁴

Because the assay requires a matched normal sample, a blood draw or additional normal tissue may be part of the testing workflow.⁴

What is the test's regulatory history?

The FDA first cleared OncoMate MSI Dx in 2021 as the first PCR-based molecular diagnostic for identifying patients with colorectal cancer who may benefit from additional testing for Lynch syndrome.^1,3 In November 2025, the FDA approved the system as a companion diagnostic to identify patients with microsatellite stable (MSS) endometrial carcinoma who may benefit from pembrolizumab plus lenvatinib (Lenvima), the company's first FDA-approved companion diagnostic.⁵ In endometrial carcinoma, the assay showed 99.0% agreement between MSS results and mismatch repair–proficient results by immunohistochemistry (IHC), according to Promega.⁴

Why does MSI status matter for pembrolizumab?

MSI results from a defective DNA mismatch repair system and is used both as a screen for Lynch syndrome and as a predictive biomarker for immune checkpoint inhibitors.³ Promega estimates that 1 in 279 people have Lynch syndrome and that 95% of them do not know it.³ In May 2017, pembrolizumab became the first drug approved by the FDA for a tissue- or site-agnostic indication, MSI-H or dMMR solid tumors.^2,6 That accelerated approval was based on 149 patients enrolled across 5 single-arm trials, 90 of whom had colorectal cancer and 59 of whom had 1 of 14 other tumor types.^2,6 At the time, MSI-H or dMMR status was largely determined by local laboratory-developed PCR or IHC tests.²

The new approval adds a standardized PCR assay to that selection step. The announcement did not provide sensitivity, specificity, or concordance data for the MSI-H solid tumor indication.¹

What are the key takeaways for oncology nurses?

• Know which test was used: MSI-H status by PCR and dMMR status by IHC both appear in the pembrolizumab indication; confirm results are documented before treatment planning.^1,2
• Anticipate a matched normal sample: The assay compares tumor DNA with normal DNA from tissue or blood, which may require an additional sample.⁴
• Set expectations on timing: Promega reports results in as little as 10 hours once the sample reaches the laboratory.⁴
• Flag possible Lynch syndrome: An MSI-H result may prompt referral for genetic counseling and germline testing, which can affect family members.³
• Support shared decision-making: Explain that eligibility for this indication rests on the tumor's MSI-H status rather than where the cancer started.²
• Prepare patients for immunotherapy: Pembrolizumab carries risks of immune-mediated adverse effects, including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.⁶

References

1. FDA approves Promega OncoMate MSI Dx Analysis System as companion diagnostic for KEYTRUDA in MSI-high solid tumors. News release. Promega. November 10, 2026. Accessed November 10, 2026. https://www.promega.com/aboutus/press-releases/global/2026/november-10-2026-fda-approves-promega-oncomate-msi-dx-analysis-system-as-companion-diagnostic/

2. FDA grants accelerated approval to pembrolizumab for unresectable or metastatic MSI-H or dMMR solid tumours. ESMO. May 2017. Accessed November 10, 2026. https://www.esmo.org/oncology-news/FDA-Grants-Accelerated-Approval-to-Pembrolizumab-for-Unresectable-or-Metastatic-MSI-H-or-dMMR-Solid-Tumours

3. Promega launches OncoMate MSI Dx Analysis System in US. News release. Promega. September 8, 2021. Accessed November 10, 2026. https://www.promega.com/aboutus/press-releases/global/2021/sept-8-2021-promega-launches-oncomate-msi-dx-analysis-system-in-us

4. OncoMate MSI Dx Analysis System. Promega. Accessed November 10, 2026. https://www.promega.com/PromegaMSI

5. DiEugenio J. FDA approves OncoMate MSI Dx as companion diagnostic for pembrolizumab/lenvatinib in MSS endometrial cancer. OncLive. November 11, 2025. Accessed November 10, 2026. https://www.onclive.com/view/fda-approves-oncomate-msi-dx-as-companion-diagnostic-for-pembrolizumab-lenvatinib-in-mss-endometrial-cancer

6. Broderick JM. A targeted role for pembrolizumab to treat certain solid tumors. Oncology Nursing News. May 24, 2017. Accessed November 10, 2026. https://www.oncnursingnews.com/view/a-targeted-role-for-pembrolizumab-to-treat-certain-solid-tumors