Dr Cercek on the FDA Approval of Dostarlimab for dMMR/MSI-H Locally Advanced Rectal Cancer

“All patients [who] have this specific genetic mutation, dMMR, [with] locally advanced rectal cancer can receive up-front immunotherapy with dostarlimab and potentially avoid standard of care, which would include chemotherapy, chemoradiation, and surgery.”

Andrea Cercek, MD, a gastrointestinal medical oncologist, section head of Colorectal Cancer, Ford Family Chair, and founder and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at Memorial Sloan Kettering Cancer Center, discussed the significance of the FDA’s accelerated approval of dostarlimab-gxly (Jemperli) in mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) locally advanced rectal cancer.

On October 19, 2026, the FDA granted accelerated approval to the PD-1 inhibitor for the treatment of adult patients with stage II or III dMMR/MSI-H locally advanced rectal cancer, as determined by an FDA-authorized test, based on data from the phase 2 AZUR-1 trial (NCT05723562), which enrolled 154 patients with previously untreated disease. Among patients evaluable by independent central review (n = 116), the sustained clinical complete response rate at 12 months (cCR12) was 47% (95% CI, 37%-56%), meeting the primary end point. Per investigator assessment (n = 144), the cCR12 rate was 68% (95% CI, 60%-76%), with no recurrences reported among responders at a median follow-up exceeding 2 years.

The approval means all patients with dMMR locally advanced rectal cancer can receive upfront dostarlimab and potentially avoid standard-of-care treatment comprising chemotherapy, chemoradiation, and surgery, Cercek explained. The approval also builds on findings from a prior investigator-initiated phase 2 study (NCT04165772) spearheaded by Cercek and colleagues at Memorial Sloan Kettering Cancer Center. Updated findings from the phase 2 study presented at the 2024 ASCO Annual Meeting showed that all evaluable patients (n = 42) achieved a cCR. With several years of follow-up now available, Cercek said that some of those patients can now be considered cured.

Delivering positive outcomes while forgoing surgery represents a crucial step for improving quality of life for patients with locally advanced rectal cancer, Cercek continued, noting that the use of biomarkers to determine dMMR/MSI-H status should guide immunotherapy decision-making.