On August 11, Roche announced the U.S. Food and Drug Administration (FDA) approval of a label expansion for the Ventana MMR RxDx Panel. The Ventana MMR RxDx Panel is the first immunohistochemistry (IHC) companion diagnostic test to aid in identifying patients whose solid tumors are deficient in DNA mismatch repair (dMMR), and who may be eligible for therapy with the PD-1 inhibitor pembrolizumab. The panel is also the first companion diagnostic test to aid in identifying patients with endometrial cancer whose tumors are proficient in DNA mismatch repair (pMMR), and who may be eligible for a combination of pembrolizumab and the tyrosine kinase inhibitor lenvatinib. The test evaluates a panel of MMR proteins in tumors to provide important treatment information to clinicians.
What is MMR?
MMR is a naturally occurring mechanism that scans DNA, correcting errors that cause disease. When MMR is deficient (dMMR), cells mutate, which can lead to cancer. While MMR deficiency is most common in endometrial cancer, other high-prevalence dMMR tumor types include gastric, colorectal, small intestine, cervical, and neuroendocrine cancers. In the United States, prevalence of dMMR across patients with solid tumors has been estimated at 14%. PD-1 inhibitors can be an effective treatment in cancers with MMR deficiency. For patients with endometrial cancer without this MMR deficiency (pMMR), PD-1 inhibitors may retain activity when combined with a tyrosine kinase inhibitor.
Approval of Label Expansion
FDA approval of the label expansion for the Ventana MMR RxDx Panel provides clinicians with access to a fully automated panel of MMR biomarkers tested by IHC. This label expansion follows the April 2021 FDA approval of the Ventana MMR RxDx Panel as the first IHC predictive test to identify patients with endometrial carcinoma patients eligible for treatment with the anti–PD-1 immunotherapy dostarlimab-gxly. That approval was expanded for the following indications on the dates below:
- August 2021: Patients with dMMR solid tumors for treatment with dostarlimab-gxly
- March 2022: Patients with dMMR solid tumors for treatment with pembrolizumab
- June 2022: Patients with pMMR solid tumors for treatment with a combination of pembrolizumab and lenvatinib
Pembrolizumab for MSI-H or dMMR Cancers
In May 2017, pembrolizumab became the first cancer treatment approved by the FDA for a tissue-agnostic indication—the FDA granted accelerated approval to the therapy for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability–high (MSI-H) or dMMR solid tumors, as determined by an FDA-approved test, whose disease has progressed following prior treatment and who have no satisfactory alternative treatment options.
Pembrolizumab for Endometrial Carcinoma
Subsequently, pembrolizumab was approved by the FDA in combination with lenvatinib for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation, as well as a single agent for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
