FDA approves Jemperli, first immunotherapy for MSI-H/dMMR locally advanced rectal cancer

On October 19, 2026, FDA granted accelerated approval to Jemperli (dostarlimab-gxly) as monotherapy for adults with previously untreated stage II or stage III locally advanced rectal cancer (LARC) that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), as determined by an FDA-authorized test.

MSI-H/dMMR tumors have defects in DNA repair that can make them particularly responsive to immune checkpoint inhibition, such as the programmed death receptor-1 (PD-1) blockade provided by Jemperli. An estimated 3% of locally advanced rectal cancers have this biomarker profile. Standard treatment for LARC typically includes chemotherapy, radiation, and surgery, which can have long-term effects on bowel, urinary, sexual, and reproductive function. Existing FDA-approved checkpoint inhibitors for MSI-H/dMMR colorectal cancer are indicated for unresectable or metastatic disease, making Jemperli the first approved immunotherapy option for this earlier-stage setting.

Approval was supported by results from the phase 2 AZUR-1 trial. Among 154 treated patients, 71% received Jemperli alone, required no additional treatment, and remained free of disease progression. Another 17% underwent surgery, while 8% received systemic therapy or radiation. Nearly half of independently evaluated patients maintained a clinical complete response for at least 12 months, and an additional one-third achieved a complete response but had not yet reached 12 months of follow-up. With a median follow-up of more than 2 years, no patients with a clinical complete response or near-complete response experienced disease progression.

FDA also reviewed findings from an investigator-led study in 50 patients, in which 93% maintained a clinical complete response for at least 12 months. No patients received chemoradiation or rectal cancer surgery as part of initial treatment, and only 1 recurrence was reported among 27 patients followed for at least 3 years. Because this is an accelerated approval based on interim results, the sponsor must continue following patients to confirm that these responses translate into lasting clinical benefit.

The safety profile was generally consistent with the established profile of Jemperli. Serious adverse reactions occurred in 20% of patients, and 3% permanently discontinued treatment because of adverse reactions. The most common adverse reactions in patients with rectal cancer were fatigue (32%), rash (22%), diarrhea (18%), and pruritus (17%). The prescribing information includes warnings for immune-mediated adverse reactions, which can be severe or fatal, as well as infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

“Standard treatment for rectal cancer has major life-changing effects. For certain types of rectal cancer, this approval represents a groundbreaking option that avoids surgery, radiation and chemotherapy. This represents a significant benefit for patients and their families,” said Angelo de Claro, MD, director of FDA’s Oncology Center of Excellence.

Sources: FDA. (2026 Oct 19). FDA grants accelerated approval to dostarlimab for locally advanced rectal cancer; FDA. (2026 Oct 19). FDA approves immunotherapy that may allow certain patients with rectal cancer to avoid chemotherapy, radiation and surgery; GSK. (2026 Oct 19). Jemperli (dostarlimab) approved in US as first and only immunotherapy for adults with MSI-H/dMMR locally advanced rectal cancer