FDA Approves Dostarlimab CDx to Detect MMR in Endometrial Cancer

The FDA has approved the VENTANA MMR RxDX panel (VENTANA), a device that determines if patients with advanced or recurrent endometrial cancer are eligible for treatment with dostarlimab-gxly (Jemperli) monotherapy, according to a press release by Roche.¹

The first of its kind immunohistochemistry predictive test is meant to be used in conjunction with dostarlimab, which is approved for patients with recurrent or advanced endometrial cancer that has progressed on or following prior treatment with platinum-containing chemotherapy.

The approval is an expansion of the current on-market VENTANA MMR IHC Panel, which is intended to the assessment of the mismatch repair (MMR) proteins, MLH1, PMS2, MSH2, and MSH6 in formalin-fixed, paraffin-embedded endometrial carcinoma tissue by light microscopy. The panel is meant to help determine the patient’s response to PD-1 targeted therapy, which can be an effective therapy for endometrial cancer. It was one of the few treatment options available for patients who progress on or after first-line therapy.

“We are excited to launch this companion diagnostic test with GSK to help recurrent or advanced endometrial cancer patients with limited treatment options,” said Thomas Schinecker, chief executive officer, Roche Diagnostics, in a press release. “This test provides clinicians with an effective tool to identify patients best suited for treatment with GSK’s Jemperli , providing a new therapeutic option for women with MMR-deficient endometrial cancer with MMR deficiency whose disease progresses on or following initial chemotherapy treatment.”

The fully automated panel provides health care providers a way of detecting MMR deficiency (dMMR) in endometrial cancer, where it is the most common. The device works by using a DNA panel of MMR biomarkers tested by immunochemistry.

Dostarlimab works by blocking PD-1 and PD-L1 pathways while helping the immune system fight cancer cells.²

The approval of the agent was based on the results from the multi-cohort, single-arm, phase 1 GARNET study (NCT02715284) of 71 patients with dMMR recurrent or advanced endometrial cancer. Overall, a complete or partial response was seen in 42.3% of patients. Additionally, 93% of those who responded had a duration of response that lasted at least 6 months.

Common adverse events (AEs) associated with dostarlimab include fatigue, nausea, diarrhea, anemia, and constipation. Immune-related AEs include pneumonitis, colitis, endocrinopathies, hepatitis, and nephritis. 

The study had an estimated enrollment of 740 participants. It has a primary endpoint of number of participants with treatment-related AEs and the number of patients with abnormal hematology parameters. Secondary outcomes included overall response rate, overall survival, progression-free survival, and immune-related objective response rate.

In order to enroll, patients must be 18 years of age and have a proven recurrent or advanced solid tumor and disease progression after treatment with available cancer therapies or be intolerant to those therapies. Patients who have had prior anti-PD-1 exposure or has a known uncontrolled central nervous system metastasis are not eligible to participate.

The device has been tested in many other cancer types in addition to endometrial cancers including breast and gastric cancers. In breast and gastric cancer, the device is meant to help identify HER2-positive disease. Anywhere between 15% to 20% of breast cancer patients harbor HER2 mutations. It was approved for this use by the FDA in July of 2020.

_REFERENCE:

_{1 Roche receives FDA approval for first companion diagnostic to identify endometrial cancer patients eligible for immunotherapy. News Release. Roche. April 23, 2021. Accessed April 23, 2021. https://bit.ly/2QPPyzo.}

_{2 FDA approves immunotherapy for endometrial cancer with specific biomarker. FDA. April 22, 2021. Accessed April 23, 2021. https://bit.ly/3dIIIod}