Dostarlimab-Gxly Diagnostic Panel Ventana MM RRxDx Panel Granted FDA Approval

The FDA has approved the Ventana MMR RxDx Panel, a companion diagnostic test to determine which patients with DNA mismatch repair deficiency (dMMR) are likely to benefit from the anti-PD-1 monotherapy dostarlimab-gxly (Jemperli), according to a press release by Roche.

DNA MMR proteins are proven biomarkers for PD-1 targeted therapy. Clinical evidence that the loss of expression of 1 or more MMR proteins increases the likelihood a patient will respond to PD-1 inhibitors. Additionally, MMR defects have been linked to mutations in the MMR proteins. Across solid tumors, the rate of dMMR has been estimated to stand at 14%.

"As the first companion diagnostic of its kind, this test can help qualify patients with solid tumours that are deficient in MMR who have progressed in their disease and who have no other suitable treatment options,” said Thomas Schinecker, chief executive officer of Roche Diagnostics, in a press release. “Based on the results of our MMR biomarker test, these patients may be eligible to receive GlaxoSmithKline’s Jemperli. We are pleased that our innovative companion diagnostic label continues to grow to serve more patients.”

In August of 2021, the FDA granted an accelerated approval to dostarlimab-gxly for the treatment of recurrent or advanced solid tumors that have progressed on or following prior treatment and have no satisfactory alternative treatment options.

Dostarlimab-gxly was granted accelerated approval based on results of the GARNET trial (NCT02715284). This phase 1 non-randomized trial had an estimated enrollment of 740 participants. Primary end points included the number of treatment-emergent adverse events (TEAEs), overall response rate (ORR), and duration of response. Secondary end points include immune-related ORR, progression-free survival (PFS), and disease control rate.

The ORR in all dMMR solid tumors was 41.6% with a complete response of 9.1% and a partial response rate of 32.5%. The median duration of response was 34.7 months with 95.4% of patients maintaining the response for at least 6 months. The ORR was 38.7% for patients in the dMMR solid tumor non-endometrial cancer cohort.

In total, 267 patients with recurrent or advanced dMMR solid tumors were evaluated for safety. The most common reported AEs were fatigue/asthenia (42%), anemia (30%), diarrhea (25%) and nausea (22%). Grade 3 or 4 adverse reactions (≥2%) were anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury. Reported grade 3 or 4 laboratory abnormalities (≥2%) included decreased lymphocytes, decreased sodium, increased alkaline phosphatase and decreased albumin.

In April of 2021, both the panel and dostarlimab-gxly were granted FDA approval for use in endometrial cancer.

_REFERENCE:

_{Roche receives FDA approval for first companion diagnostic to identify dMMR solid tumour patients eligible for anti-PD-1 immunotherapy. News release. Roche. August 18, 2021. Accessed August 19, 2021. https://bit.ly/3z1kPk5.}