FDA approves first immunotherapy for locally advanced rectal cancer, potentially sparing patients from surgery and chemo

The FDA has granted accelerated approval to dostarlimab-gxly (Jemperli, GSK) — making it the first and only immunotherapy approved for adults with stage II or III mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) locally advanced rectal cancer. The approval marks a significant shift from the standard-of-care approach, which typically involves chemotherapy, radiation, and surgery — treatments that can cause permanent bowel, bladder, sexual, and fertility complications, and sometimes result in a lifelong colostomy.

The decision was supported by the phase 2 AZUR-1 trial (n = 154), in which patients received 500 mg of dostarlimab IV every 3 weeks for up to nine cycles. Among investigator-evaluable patients, 68% achieved a sustained clinical complete response at 12 months (cCR12), and 71% avoided any further oncological treatment. Additional support came from a Memorial Sloan Kettering Cancer Center phase 2 study (n = 50), where the cCR12 rate was 93% and the overall response rate was 100%, with only one recurrence among patients followed for at least 3 years. The drug was well tolerated, with fatigue (32%), rash (22%), and diarrhea (18%) as the most common side effects.

By the Numbers:

• 71% of AZUR-1 patients remained disease-free on dostarlimab alone
• 68% achieved sustained complete response at 12 months (investigator assessment)
• 93% cCR12 rate in the MSK phase 2 study (n = 50)
• Only 1 recurrence among 27 patients followed ≥3 years in the MSK study
• dMMR/MSI-H tumors account for ~5–10% of rectal cancers

Why it matters: For a subset of rectal cancer patients with a specific tumor biomarker, this approval opens the door to a surgery-free, chemo-free path to remission — a meaningful quality-of-life benefit. Continued approval hinges on confirmatory trial data to verify long-term benefit.