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

The European Union (EU) has certified the MMR IHC Panel pharmDx (Dako Omnis) under EU in vitro diagnostic regulation as a class C companion diagnostic to identify patients with mismatch repair–deficient (dMMR) colorectal cancer (CRC) who may be eligible for treatment with nivolumab (Opdivo) in combination with ipilimumab (Yervoy).1

This certification follows the FDA approval of the MMR IHC Panel pharmDx as a companion diagnostic for the same indication on August 20, 2025.2

The MMR pathway plays a critical role in correcting DNA replication errors and maintaining genomic stability.1 Loss of function in key MMR proteins, such as MLH1, PMS2, MSH2, and MSH6, results in dMMR disease, which is associated with an increased mutational burden, tumorigenesis, and accumulation of neoantigens and render dMMR tumors to be more susceptible to immunotherapy.

MMR IHC Panel pharmDx is an immunohistochemical panel developed and validated to detect the loss of function of any of the four MMR proteins in formalin-fixed, paraffin-embedded colorectal cancer tissue. The assay is approved for exclusive use with the Agilent Dako Omnis automated staining solution and is indicated to identify patients with dMMR CRC who may be eligible for treatment with nivolumab in combination with ipilimumab, which demonstrated efficacy in the phase 3 CheckMate-8HW trial (NCT04008030).3

“The approval of MMR IHC Panel pharmDx will provide physicians in Europe with critical information to inform treatment decisions for patients with dMMR [CRC],” Nina Green, vice-president and general manager of the Clinical Diagnostics Division at Agilent, remarked in a news release.1 “This endorsement underscores Agilent’s leadership in the development of companion diagnostics for groundbreaking therapies.”

Role of Nivolumab/Ipilimumab

Patients in the phase 3 CheckMate-8HW study were randomly assigned in a 2:2:1 ratio to receive either nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy with or without targeted agents.3 In the combination arm, patients were given nivolumab at 240 mg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab 480 mg every 4 weeks. Those assigned to nivolumab monotherapy received 240 mg every 2 weeks for 6 doses, then transitioned to 480 mg every 4 weeks.

The primary end points were progression-free survival (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.

At the data cutoff date of August 28, 2024, the median follow-up was 47.0 months (IQR, 38.4-53.2). 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). The median PFS was not reached in the combination arm (95% CI, 53.8-not estimable [NE]) vs 39.3 months (95% CI, 22.1-NE) with nivolumab monotherapy.

With regard to safety, 81% (n = 352) and 71% (n = 351) of patients experienced treatment-related adverse effects (TRAEs) in the nivolumab plus ipilimumab and nivolumab monotherapy arms, respectively. Grade or higher 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.

References

1. Agilent’s mmr ihc panel pharmdx (dako omnis) receives european ivdr certification as a companion diagnostic test for colorectal cancer. News Release. Agilent Technologies Inc. September 2, 2025. https://www.investor.agilent.com/news-and-events/news/news-details/2025/Agilents-MMR-IHC-Panel-pharmDx-Dako-Omnis-Receives-European-IVDR-Certification-as-a-Companion-Diagnostic-Test-for-Colorectal-Cancer/default.aspx
2. 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
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