FDA Approves VENTANA MMR RxDx as Companion Diagnostic for Dostarlimab in Endometrial Cancer

FDA

The FDA has approved the VENTANA MMR RxDx panel as a companion diagnostic assay to determine eligibility for dostarlimab-gxly (Jemperli) as a treatment for patients with advanced or recurrent endometrial cancer whose tumors are mismatch repair deficient (dMMR).¹

The companion diagnostic is designed to provide clinicians with a standard testing option utilizing a comprehensive panel of dMMR biomarkers, which is tested via immunohistochemistry (IHC). The VENTANA MMR RxDx assay’s approval allows access to a fully automated MMR test that will classify patients with endometrial cancer who may be able to receive dostarlimab, which received accelerated approval by the FDA on April 22, 2021.

“We are excited to launch this companion diagnostic test with [GlaxoSmithKline] to help recurrent or advanced endometrial cancer patients with limited treatment options,” said Thomas Schinecker, CEO of Roche Diagnostics, the developer of the assay. “This test provides clinicians with an effective tool to identify patients best suited for treatment with GlaxoSmithKline’s] Jemperli, providing a new therapeutic option for women with MMR-deficient endometrial cancer whose disease progresses on or following initial chemotherapy treatment.”

The VENTANA MMR RxDx assay is a label expansion of the company’s currently available VENTANA MMR IHC Panel, Roche noted in a press release. VENTANA MMR RxDx is a qualitative IHC test designed for use in assessing the mismatch repair (MMR) proteins: MLH1, PMS2, MSH2 and MSH6. The proteins are assessed in formalin-fixed, paraffin-embedded (FFPE) endometrial carcinoma tissue through light microscopy.

Additionally, the OptiView DAB IHC Detection Kit is used for MLH1, MSH2 and MSH6, and the OptiView DAB IHC Detection Kit with the OptiView Amplification Kit is used for PMS2 on a VENTANA BenchMark ULTRA instrument, the company stated.

Dostarlimab, a PD-1 inhibitor, received indication as a treatment for patients with recurrent or advanced endometrial cancer that has progressed on or following prior platinum-based chemotherapy and whose cancers are dMMR, as determined by an FDA-approved test.^2,3 The approval was granted through the FDA’s Real-Time Oncology Review pilot program.

The decision was based on data from the dMMR endometrial cancer cohort of the multicenter, single-arm, multiple parallel-cohort, open-label GARNET trial.

In the study, investigators tested dostarlimab monotherapy in expansion cohorts across multiple tumor types. Patients who were eligible for enrollment were treated with dostarlimab at 500 mg of intravenous (IV) every 3 weeks for 4 cycles followed by 1000 mg IV every 6 weeks until disease progression.

The study consists of dose-finding (part 1), fixed-dose safety run-in (part 2A), and expansion cohorts (part 2B). The expansion cohort included 5 groups: dMMR endometrial cancer (A1; n = 129), MMRp endometrial cancer (A2; n = 161), non–small cell lung cancer (E), nonendometrial dMMR/MSI-H cancer (F), and platinum-resistant ovarian cancer (G).

The coprimary end points are objective response rate (ORR) and duration of response (DOR) by blinded independent central review (BICR) RECIST v1.1 criteria. Additionally, immune-related (ir)RECIST criteria served as a prespecified secondary end point, due to standard RECIST criteria potentially undervaluing the clinical benefit of immunotherapy.

Eligibility criteria in cohorts A1 and A2 included disease progression on or after platinum-doublet therapy, have received 2 or fewer prior lines of therapy for recurrent or advanced disease, and have measurable disease at baseline. Furthermore, patients were required to have PD-L1–naïve disease and confirmed MMR/MSI disease by MMR IHC results.

Results that led to the approval showed that dostarlimab led to a 42.3% ORR in 71 patients with dMMR recurrent or advanced endometrial cancer, which included a 12.7% complete response rate and a 29.6% partial response rate.

The DOR was at least 6 months for 93.3% of responders, and the median DOR was not reached at a median follow-up of 14.1 months (2.6-22.4+).

Regarding safety data for the approval of dostarlimab, GlaxoSmithKline, the PD-1 inhibitor’s developer, noted that among 104 patients evaluable for safety, the most common (≥20%) adverse events (AEs) included fatigue (48%), nausea (30%), diarrhea (26%), anemia (24%), and constipation (20%).

The most common (≥2%) grade 3/4 AEs included anemia and increase in alanine transaminase levels. Discontinuations of dostarlimab due to AEs occurred in 5 (4.8%) of patients, and no drug-related deaths occurred.

References

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.
2. FDA approves immunotherapy for endometrial cancer with specific biomarker. News release. FDA. April 22, 2020. Accessed April 22, 2020. https://prn.to/3ngdVSL
3. FDA grants accelerated approval for GSK’s Jemperli (dostarlimab-gxly) for women with recurrent or advanced dMMR endometrial cancer. News release. GlaxoSmithKline. April 22, 2021. Accessed April 22, 2021. https://bit.ly/3tIUqVj