FDA Green Lights First Companion Diagnostic for Dostarlimab in dMMR Solid Tumors

The FDA has approved the VENTANA MMR RxDx panel as the first companion diagnostic test to assist in identifying patients with solid tumors that are DNA mismatch repair deficient who may be eligible to receive the anti–PD-1 therapy dostarlimab-gxly, which was recently granted an accelerated approval by the agency.



The FDA has approved the VENTANA MMR RxDx panel as the first companion diagnostic test to assist in identifying patients with solid tumors that are DNA mismatch repair deficient (dMMR) who may be eligible to receive the anti–PD-1 therapy dostarlimab-gxly (Jemperli), which was recently granted an accelerated approval by the agency.1

Dostarlimab is now indicated for adult patients with dMMR recurrent or advanced solid tumors who have progressed on or after prior treatment and who have no satisfactory alternative options.2 The regulatory decision was supported by collective findings from the dMMR endometrial cancer cohort A1 and the dMMR solid-tumor, non-endometrial cancer cohort F of the ongoing phase 1 GARNET trial (NCT02715284).

The agent resulted in an overall response rate (ORR) of 41.6% (95% CI, 34.9%-48.6%) per blinded independent central review and RECIST v1.1 criteria, with a complete response rate of 9.1% and a partial response rate of 32.5%. Moreover, the median duration of response (DOR) experienced with the immunotherapy was 34.7 months (range, 2.6-35.8+). Notably, 95.4% of patients experienced a DOR that persisted for 6 months or longer.

The assay provides access to a fully automated panel of MMR biomarkers that are examined via immunohistochemistry, allowing for stronger clinical decisions for patients with cancer.

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

The assay examines a panel of MMR proteins in tumors. MMR is a naturally occurring mechanism that scans our DNA and corrects errors that result in disease. When deficient, MMR causes cells to mutate, which can then lead to cancer. MMR deficiency is frequently observed in endometrial cancer, but also has a high prevalence in gastric cancer, colorectal cancer (CRC), small intestine cancer, cervical cancer, and neuroendocrine cancers.

The VENTANA MMR IHC panel was previously launched in 2017 as an FDA Class II device to assist in the identification of Lynch syndrome in patients with CRC.3 The panel looks at the following 4 MMR proteins: MLH1, MSH2, MSH6, and PMS2. The panel also comprises the VENTANA BRAF V600E (VE1) Mouse Monoclonal Antibody. The combination of the 5 antibodies is used to assist in Lynch syndrome identification, which is a predisposition for CRC and other malignancies. Notably, the VENTANA MMR RxDx panel includes the same antibodies, except for the VENTANA BRAF V600E (VE1).

Dostarlimab is under evaluation as a monotherapy in the ongoing, multicenter, non-randomized, multiple parallel-cohort, open-label GARNET trial. Part 2B of the trial included 5 expansion cohorts: dMMR/microsatellite instability–high endometrial cancer (cohort A1), mismatch repair proficient/microsatellite stable endometrial cancer (cohort A2), non–small cell lung cancer (cohort E), dMMR/MSI-H non-endometrial or POLE-mutated solid tumor (basket cohort F), and platinum-resistant ovarian cancer without BRCA mutations (cohort G).

To enroll to cohort A, patients must have progressed on or following prior treatment with a platinum-containing regimen. To be eligible for inclusion on cohort F, patients needed to have progressed after systemic therapy and not have any satisfactory alternative options. Patients with CRC were required to have progressive disease after, or have been intolerant to, fluoropyrimidine, oxaliplatin, and irinotecan, for inclusion.

Participants received intravenous dostarlimab at a dose of 500 mg once every 3 weeks for a total of 4 doses and this was followed by a dose of 1000 mg that was given once every 6 weeks. Patients were administered treatment until disease progression or unacceptable toxicity.

The adverse effects (AEs) that were most frequently experienced by 20% or more of the patients with dMMR solid tumors included fatigue/asthenia, anemia, diarrhea, and nausea.4 The most common grade 3 or 4 toxicities, reported in 2% or more of patients, comprised anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury.

Dostarlimab-associated immune-mediated AEs included pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and dermatologic toxicity.


  1. 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 18, 2021. https://bit.ly/3gdP7sg
  2. GSK receives FDA accelerated approval for JEMPERLI (dostarlimab-gxly) for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumors. News release. GlaxoSmithKline. August 17, 2021. Accessed August 18, 2021. https://bit.ly/3yVSiMN
  3. VENTANA MMR RxDx panel (US FDA approved). Roche website. Accessed August 18, 2021. https://bit.ly/3mfBYTs
  4. FDA grants accelerated approval to dostarlimab-gxly for dMMR advanced solid tumors. News release. FDA. August 17, 2021. Accessed August 18, 2021. https://bit.ly/3ggqoDE
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