FDA approval of dostarlimab may allow certain patients with rectal cancer to avoid surgery

The FDA on Oct. 19, 2026, granted accelerated approval to dostarlimab-gxly (Jemperli, GSK) as a single agent for adults with previously untreated stage II or III locally advanced rectal cancer that is mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H), as determined by an FDA-authorized test.¹

The agency said the PD-1 inhibitor may allow some of these patients to avoid chemotherapy, radiation, and surgery. In its announcement, the FDA noted that neoadjuvant chemoradiation can affect bowel, urinary, and sexual function as well as fertility, and that rectal surgery carries risks that include anastomotic leaks and, for some patients, permanent colostomy.¹

“Standard treatment for rectal cancer has major life-changing effects,” Angelo de Claro, MD, director of the FDA’s Oncology Center of Excellence, said in the announcement. “For certain types of rectal cancer, this approval represents a groundbreaking option that avoids surgery, radiation and chemotherapy.”¹

The FDA cited published estimates that about 3% of locally advanced rectal cancers are dMMR or MSI-H.¹

What the trial results showed

The approval rests on interim results from AZUR-1 (NCT05723562), a phase 2 study of dostarlimab alone in 154 patients with previously untreated dMMR or MSI-H locally advanced rectal cancer. Patients received up to nine doses, given every 3 weeks over 6 months.¹

After a median follow-up of more than 2 years, almost three-fourths of patients had not needed surgery, radiotherapy, or chemotherapy, according to the FDA. The agency said longer follow-up is needed to understand the duration of response and how often the cancer returns.¹

An earlier study at Memorial Sloan Kettering Cancer Center (NCT04165772) evaluated dostarlimab alone in 50 patients with previously untreated dMMR or MSI-H locally advanced rectal cancer. None had detectable signs of cancer after treatment, and 93% maintained that cancer-free status for at least 12 months. Of 27 patients followed for at least 3 years, one had a recurrence, which occurred in the same area.¹

Where gastroenterology fits in

Dostarlimab will be given by oncologists, but the care pathway the approval opens touches gastroenterology at several points, beginning with tumor testing. The indication requires MMR or MSI status to be established by an FDA-authorized test.¹ In GSK’s announcement, Michael Sapienza, CEO of the Colorectal Cancer Alliance, said biomarker testing at diagnosis “will be essential to identifying patients who may be eligible.”²

That testing is not new to the field. Since 2014, the US Multi-Society Task Force on Colorectal Cancer, which includes the AGA, has recommended testing all newly diagnosed colorectal cancers for evidence of MMR deficiency, primarily as a strategy to identify Lynch syndrome.³

The potential payoff is organ preservation. The FDA framed the benefit in terms of sparing patients chemoradiation and rectal surgery, along with the surgical risks of anastomotic leaks and permanent colostomy.¹

Safety and regulatory status

Dostarlimab can cause the immune system to attack healthy organs and tissues, and these reactions can be severe or fatal, the FDA said. The most common side effects in patients treated for this type of rectal cancer, reported in at least 15%, were fatigue, rash, diarrhea, and itching.¹

The application received priority review, and dostarlimab holds breakthrough therapy designation for this indication. The FDA said the approval was the 11th under the Commissioner’s National Priority Voucher pilot program and that the review was completed nearly 4 months ahead of schedule.¹

Because this is an accelerated approval based on interim trial results, GSK must continue following patients to show that the responses translate into lasting clinical benefit.¹ GSK said full interim AZUR-1 data will be presented at the European Society for Medical Oncology Congress this month.²

References

1. US Food and Drug Administration. FDA approves immunotherapy that may allow certain patients with rectal cancer to avoid chemotherapy, radiation and surgery. News release. October 19, 2026. Accessed October 20, 2026.

2. GSK. Jemperli (dostarlimab-gxly) approved in US as first and only immunotherapy for adults with MSI-H/dMMR locally advanced rectal cancer. News release. October 19, 2026. Accessed October 20, 2026.

3. Giardiello FM, Allen JI, Axilbund JE, et al. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2014;147(2):502-526.