FDA grants accelerated approval to dostarlimab for dMMR rectal cancer

On October 19, 2026, the FDA granted accelerated approval to GSK's PD-1 inhibitor dostarlimab (Jemperli) for adults with stage II and III dMMR or MSI-H locally advanced rectal cancer. Based on the phase II AZUR-1 trial demonstrating complete response rates up to 68% and zero recurrences after two years of follow-up, this first-in-class immunotherapy approval enables eligible patients—comprising 3% to 10% of rectal cancer cases—to avoid surgery, radiation, and colostomies.

FDA approval of dostarlimab

• ▪Continued FDA approval for dostarlimab in stage II and III dMMR or MSI-H locally advanced rectal cancer requires GSK to confirm clinical benefit in confirmatory studies such as the AZUR-2 trial.
• ▪The FDA granted accelerated approval to GSK's dostarlimab (Jemperli) on October 19, 2026, as the first immunotherapy for adults with stage II and III dMMR or MSI-H locally advanced rectal cancer.
• ▪The FDA reviewed dostarlimab's application under Project Orbis and a National Priority Voucher, granting approval nearly four months ahead of the PDUFA target date.

AZUR-1 trial efficacy results

• ▪In the AZUR-1 trial of dostarlimab, the overall objective response rate was 79% by central review and 82% by investigator review, with no disease recurrences reported among responders after a median follow-up of over two years.
• ▪In the phase II AZUR-1 trial of 154 patients, 47% of 116 evaluable patients achieved a sustained clinical complete response at 12 months by central review, and 68% of 144 evaluable patients by investigator review.

AZUR-1 trial safety profile

• ▪In the AZUR-1 trial, serious adverse reactions occurred in 20% of patients receiving dostarlimab, and 3% of patients permanently discontinued treatment due to adverse events.
• ▪The most common adverse reactions to dostarlimab in the AZUR-1 trial were fatigue (32%), rash (22%), diarrhea (18%), and pruritus (17%).

Findings from the Memorial Sloan Kettering study

• ▪In a Memorial Sloan Kettering Cancer Center study led by Andrea Cercek, five babies were born to patients who received dostarlimab monotherapy, avoiding radiation-induced menopause and infertility.
• ▪An earlier 50-patient study at Memorial Sloan Kettering Cancer Center demonstrated a 93% clinical complete response rate at 12 months with dostarlimab monotherapy, with only one local recurrence observed among 27 patients followed for three years.

Characteristics of dMMR rectal cancer

• ▪Defects in mismatch repair lead cancer cells to accumulate DNA errors and produce foreign proteins that make dMMR and MSI-H rectal tumors recognizable to PD-1 inhibitor immunotherapies like dostarlimab.
• ▪Mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) biomarkers occur in approximately 3% to 10% of locally advanced rectal cancers.

Complications of standard rectal cancer treatments

• ▪Standard pelvic radiation and surgery for rectal cancer frequently cause infertility, impaired pelvic function, and long-term bowel, urinary, or sexual dysfunction in young patients.
• ▪Standard surgical intervention for locally advanced rectal cancer requires permanent colostomy creation in approximately 30% of patients.