FDA Approves MMR IHC Panel pharmDx as a Companion Diagnostic for Nivolumab/Ipilimumab in MSI-H/dMMR CRC

The FDA has approved the MMR IHC Panel pharmDx (Dako Omnis) as a companion diagnostic to identify patients with mismatch repair–deficient (dMMR) colorectal cancer (CRC) who may be eligible for treatment with nivolumab (Opdivo) as monotherapy or in combination with ipilimumab (Yervoy).1

This approval allows the assay to be used exclusively with the Agilent Dako Omnis automated staining solution. The panel is the only FDA-approved immunohistochemistry (IHC)-based companion diagnostic designed to detect loss of function of the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6 in formalin-fixed paraffin-embedded (FFPE) CRC tissue. Of note, the MMR pathway corrects DNA replication errors to maintain genomic stability.

“This approval marks an important step forward in the ongoing effort to improve [CRC] care,” Nina Green, vice president and general manager of Agilent’s Clinical Diagnostics Division, stated in a news release. “Our new CDx product offers health care providers an additional tool to identify [dMMR] in patients, complementing existing options and enhancing the ability to tailor immunotherapy treatments. By providing more choices, we aim to support better tumor control and potentially improve progression-free survival [PFS], ultimately contributing to patient care and well-being.”

The FDA approval of the MMR IHC Panel pharmDx comes after the April 8, 2025, FDA approval of nivolumab plus ipilimumab for patients 12 years and older with dMMR or microsatellite instability–high (MSI-H) unresectable or metastatic CRC.2

Notably, the approval of the nivolumab plus ipilimumab combination was supported by data from the phase 3 CheckMate-8HW trial (NCT04008030), which evaluated first-line nivolumab plus ipilimumab in patients with dMMR/MSI-H metastatic CRC. At the data cutoff date of August 28, 2024, the median follow-up was 47.0 months (IQR, 38.4-53.2).3 Data revealed that PFS was significantly improved and clinically meaningful when patients received nivolumab plus ipilimumab compared with nivolumab alone (HR, 0.62; 95% CI, 0.48-0.81; P = .0003). Furthermore, the median PFS was not reached with the combination (95% CI, 53.8-not estimable [NE]) compared with 39.3 months (95% CI, 22.1-NE) with the monotherapy.

Based on safety data, 81% (n = 285 of 352) and 71% (n = 249 of 351) of patients experienced treatment-related adverse effects (TRAEs) in the nivolumab plus ipilimumab and nivolumab monotherapy arms, respectively. Grade 3/4 TRAEs occurred in 22% and 14% of patients from the respective arms. Treatment-related deaths occurred in 3 patients, with 1 due to myocarditis and 1 due to pneumonitis in the combination arm, and 1 due to pneumonitis in the monotherapy arm.

Delving Into the CheckMate-8HW Study Design

Part 2 of the open-label, international study included patients who had not previously received immunotherapy for histologically confirmed unresectable, recurrent, or metastatic CRC.3,4 Patients included in the study were also required to have known tumor MSI-H or dMMR status, and an ECOG performance status of 0 or 1.4 Patients were not included in the study if they had active, known, or suspected autoimmune disease; history of interstitial lung disease or pneumonitis; or history of a positive test for HIV or known immunodeficiency syndrome.

Patients included in the study were randomly assigned 2:2:1 to receive nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy with or without targeted therapies.3 Specifically, patients treated with nivolumab plus ipilimumab received nivolumab at a dose of 240 mg plus ipilimumab at 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab at 480 mg every 4 weeks. Patients in the nivolumab monotherapy arm were treated with 240 mg every 2 weeks for 6 doses and subsequently, 480 mg every 4 weeks.

The dual independent primary end points were PFS by blinded independent central review (BICR) with the nivolumab plus ipilimumab combination vs chemotherapy, and PFS by BICR with the combination vs nivolumab alone. Secondary end points included overall response rate and overall survival.4

References

1. Agilent MMR IHC panel pharmDx (Dako Omnis) receives FDA approval as a companion diagnostic test for colorectal cancer. News release. Agilent. August 20, 2025. Accessed August 20, 2025. https://www.agilent.com/about/newsroom/presrel/2025/20aug-25026.html
2. FDA approves nivolumab with ipilimumab for unresectable or metastatic MSI-H or dMMR colorectal cancer. FDA. April 8, 2025. Accessed August 20, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-ipilimumab-unresectable-or-metastatic-msi-h-or-dmmr-colorectal-cancer
3. André T, Elez E, Lenz HJ, et al. Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial. Lancet. 2025;405(10476):383-395. doi:10.1016/S0140-6736(24)02848-4
4. A study of nivolumab, nivolumab plus ipilimumab, or investigator’s choice chemotherapy for the treatment of participants with deficient mismatch repair (dMMR)/microsatellite instability high (MSI-H) metastatic colorectal cancer (mCRC) (CheckMate 8HW). ClinicalTrials.gov. Updated June 18, 2025. Accessed August 20, 2025. https://clinicaltrials.gov/study/NCT04008030