Dostarlimab Received FDA Approval for dMMR-Positive Cancers

On August 17, 2021, the FDA (US Food and Drug Administration) granted accelerated approval to the immunotherapy drug dostarlimab-gxly (Jemperli, GlaxoSmithKline LLC) for adults with recurrent or advanced solid (organ) cancers carrying the genetic defect "DNA mismatch repair deficiency" (dMMR), which had progressed after prior treatments and had no satisfactory treatment options.

The FDA simultaneously approved the VENTANA MMR RxDx Panel as a companion diagnostic device to identify eligibility for dostarlimab-gxly treatment.

Dostarlimab had previously received FDA approval on April 22, 2021 for treating dMMR-positive recurrent or advanced endometrial (uterine) cancer (see the relevant approval).

• IMPORTANT DEVELOPMENT: 100 Percent Response to Preoperative Immunotherapy in Rectal Cancer

What Is dMMR?

dMMR (mismatch repair deficient) is an abnormality affecting proper DNA repair inside cells and, in tumor tissue, is identified by genetic tests .

What Is Dostarlimab?

Dostarlimab (Jemperli) binds to PD-1, blocking this molecule's interaction with PD-L1 and PD-L2; as an immune checkpoint inhibitor , it is a next-generation immunotherapy.

PD-1 is found on the surface of immune cells, while PD-L1 and PD-L2 are found on immune cells and some cancer cells.

Blocking the PD-1 and PD-L1-L2 interaction on cell surfaces helps the body's immune system fight cancer cells. This immunotherapy was specifically designed to target dMMR endometrial cancer.

The Garnet Study

Dostarlimab's efficacy was evaluated in GARNET, a nonrandomized, multicenter, open-label, multicohort clinical trial. The efficacy population consisted of 209 patients whose disease had progressed following systemic therapy and who had no satisfactory alternative treatment, or who had advanced dMMR-positive solid tumors.

The primary efficacy endpoints, determined by blinded independent central review according to RECIST 1.1, were overall response rate and duration of response.

• The overall response rate was 41.6%, including 9.1% complete responses and 32.5% partial responses (95% CI: 34.9, 48.6).
• Median duration of response was 34.7 months (range 2.6, 35.8+), with a response duration of ≥ 6 months in 95.4% of these patients.

In this dMMR-positive patient group, the most common (≥20%) side effects with dostarlimab were fatigue/asthenia, anemia, diarrhea and nausea. The most common grade 3 or 4 adverse events were anemia, fatigue/asthenia, increased transaminases, sepsis and acute kidney injury. Immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and dermatological toxicity, are also associated with dostarlimab-gxly.

The recommended dostarlimab dose is 500 mg every 3 weeks for the first 1 to 4 cycles, as an intravenous infusion over 30 minutes. Subsequent dosing, starting 3 weeks after dose 4, is 1,000 mg every 6 weeks.