The U.S. Food and Drug Administration (FDA) has approved Roche's VENTANA MMR RxDx panel, a novel companion diagnostic device designed to identify patients with advanced or recurrent endometrial cancer who may benefit from treatment with dostarlimab-gxly (Jemperli). This approval marks a significant advancement in precision medicine for gynecologic oncology.
The VENTANA panel is the first immunohistochemistry predictive test specifically developed to determine eligibility for dostarlimab monotherapy in patients whose disease has progressed on or following platinum-containing chemotherapy. The diagnostic works by detecting mismatch repair deficiency (dMMR), a biomarker particularly common in endometrial cancers.
"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 of Roche Diagnostics. "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 whose disease progresses on or following initial chemotherapy treatment."
Dostarlimab's Accelerated Approval
Concurrently, the FDA granted accelerated approval to dostarlimab for the treatment of patients with recurrent or advanced dMMR endometrial cancer that has progressed on or following prior treatment with platinum-containing chemotherapy.
Dostarlimab is a PD-1 inhibitor that works by blocking PD-1 and PD-L1 pathways, helping the immune system recognize and fight cancer cells. The approval represents an important new option for patients with limited treatment alternatives.
"Today's approval of Jemperli is evidence of the FDA's progress in applying precision medicine to expand treatment options for patients with cancer," said Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence. "This immunotherapy was specifically studied to target dMMR endometrial cancer and leverages scientific knowledge surrounding the mechanism of immunotherapy response in this unmet medical need population."
The GARNET Trial: Efficacy and Safety Data
The approval was based on results from the multi-cohort, single-arm, phase 1 GARNET study (NCT02715284), which evaluated dostarlimab in patients with various advanced solid tumors. Among 71 patients with dMMR recurrent or advanced endometrial cancer, 42.3% achieved a complete or partial response. Notably, 93% of those who responded maintained their response for at least 6 months, demonstrating the durability of the treatment effect.
In the treatment protocol, patients received 500 mg of dostarlimab once every three weeks for four doses, followed by 1000 mg once every six weeks until disease progression.
Updated results presented at the European Society for Medical Oncology 2020 Congress showed that in an expanded cohort of 103 patients with dMMR tumors, the objective response rate was 44.7%, including 11 complete responses and 35 partial responses. The disease control rate reached 57.3%.
Safety Profile
The safety profile of dostarlimab appears consistent with other approved PD-1 inhibitors. In the safety population of 104 patients with dMMR disease, only 2% discontinued treatment due to treatment-related adverse events (TRAEs).
The most common TRAEs included:
- Asthenia (15%)
- Diarrhea (15%)
- Fatigue (14%)
- Nausea (13%)
Other potential immune-related adverse events associated with dostarlimab include pneumonitis, colitis, endocrinopathies, hepatitis, and nephritis. No grade 5 (fatal) events were reported in the trial.
The VENTANA MMR RxDx Panel
The newly approved diagnostic is an expansion of the current VENTANA MMR IHC Panel. It assesses mismatch repair proteins—MLH1, PMS2, MSH2, and MSH6—in formalin-fixed, paraffin-embedded endometrial carcinoma tissue by light microscopy.
The fully automated panel provides healthcare providers with a standardized method for detecting dMMR in endometrial cancer using a panel of MMR biomarkers tested by immunohistochemistry. This approach helps identify patients who are most likely to respond to PD-1 targeted therapy.
Beyond endometrial cancer, the VENTANA technology has been tested in other cancer types, including breast and gastric cancers, where it helps identify HER2-positive disease.
Clinical Implications
Endometrial cancer is the most common gynecologic malignancy in the United States, and patients with recurrent or advanced disease have historically had limited treatment options. The approval of both dostarlimab and its companion diagnostic represents a significant step forward in addressing this unmet need.
For patients whose disease progresses after first-line platinum-based chemotherapy, the ability to identify those with dMMR status who may benefit from immunotherapy could significantly impact clinical outcomes and quality of life.
Full approval for dostarlimab is contingent upon further clinical trials to verify and describe its clinical benefit in this setting. Meanwhile, the availability of a reliable companion diagnostic ensures that the therapy can be appropriately targeted to those most likely to respond.
The approvals highlight the growing importance of biomarker-driven treatment approaches in oncology and the value of companion diagnostics in guiding precision medicine strategies for difficult-to-treat cancers.
