FDA grants accelerated approval to dostarlimab for locally advanced rectal cancer

On October 19, 2026, the Food and Drug Administration granted accelerated approval to dostarlimab (Jemperli, GSK) for adults with Stage II/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 for solid tumors. The FDA said full prescribing information for Jemperli will be posted on Drugs@FDA.

The label

The FDA said the recommended dostarlimab dose is 500 mg every three weeks until disease progression or unacceptable toxicity, for up to nine cycles.

The FDA said the prescribing information includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

The AZUR-1 trial

The FDA said efficacy was evaluated in AZUR-1 (NCT05723562), a multicenter, single-arm, open-label trial in 154 patients with previously untreated, histologically confirmed, MSI-H/dMMR, Stage II/III LARC. Patients received dostarlimab 500 mg intravenously every 3 weeks for nine cycles unless unacceptable toxicity or disease progression occurred.

Tumor response was assessed using a combination of endoscopy, rectal MRI, and CT scans at Week 6, Week 12, and approximately 3 weeks after completing treatment. Patients who achieved a clinical complete response (cCR) at either of the first two post-treatment assessments entered a non-operative management period. In that period, patients were closely monitored for recurrence every 4 months for the first 2 years and every 6 months thereafter.

The FDA said the primary efficacy outcome measure was sustained cCR for 12 months (cCR12) per independent central review (ICR), measured from the first disease assessment after the last dose of dostarlimab where cCR was observed. Additional efficacy outcome measures included cCR12 based on investigator assessments and objective response rate (ORR) as per ICR and per investigator.

The results the FDA reported

The FDA reported what happened to the 154 treated patients:

110 (71%) were treated with dostarlimab alone, did not receive any additional form of treatment, and did not experience disease progression.
26 (17%) underwent surgery, with or without additional systemic therapy or radiation.
13 (8%) received additional systemic therapy or radiation.
1 (0.6%) had progressive disease without further treatment.
4 (2.5%) withdrew or were lost to follow-up.

On the primary outcome, the FDA said that in 116 ICR-evaluable patients the cCR12 was 47% (95% CI: 27%, 56%). The ORR per ICR was 79% (95% CI: 71%, 85%).

The FDA listed the investigator-assessed figures separately. In 144 investigator-evaluable patients, the cCR12 rate was 68% (95% CI: 60%, 76%) and the ORR was 82% (95% CI: 75%, 88%).

The FDA also said 38 (33%) patients achieved cCR by ICR and had less than 12 months of follow-up at the time of the data cutoff, and 44 (38%) patients had near CR. With a median follow up of 26.3 months, none of the patients with cCR12, cCR, or near CR experienced disease progression, the FDA said.

A second trial in the FDA review

The FDA said it also reviewed an investigator-led, multicenter, single-arm, open-label trial (NCT04165772) that assessed dostarlimab 500 mg intravenously every three weeks for nine cycles in 50 patients with previously untreated, MSI-H/dMMR, Stage II/III LARC. In that trial the cCR12 rate was 93% (95% CI: 82%, 99%) and the ORR was 100% (95% CI: 93%, 100%).

The FDA said no patients in that trial received chemoradiation and/or rectal cancer surgery as part of the treatment of LARC. Of the 27 patients followed for at least 3 years, 1 patient had a local recurrence treated with lymphadenectomy, 1 patient withdrew, and 1 patient died unrelated to disease under study.

The FDA review process

The FDA said the review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. The FDA collaborated with Health Canada, Israel's Ministry of Health, Switzerland's Swissmedic, and the United Kingdom's Medicines and Healthcare products Regulatory Agency. The application reviews are ongoing at the other regulatory agencies.

The review used the Real-Time Oncology Review (RTOR) program and the Assessment Aid, a voluntary submission from the applicant. The FDA approved the application 4 months ahead of the FDA goal date. The application is part of the FDA Commissioner's National Priority Review Voucher (CNPV) pilot program. The FDA said the application was granted priority review and that dostarlimab received breakthrough therapy designation.

The accelerated approval pathway

The approval notice does not describe a confirmatory trial. The FDA's page on Accelerated Approval gives an example of approval based on tumor shrinkage and says the drug company will still need to conduct studies to confirm that tumor shrinkage actually predicts that patients will live longer. The page says that where confirmatory trials verify clinical benefit, the FDA will generally terminate the requirement.