On October 19, 2026, the U.S. Food and Drug Administration (FDA) granted an accelerated approval to the PD-1 inhibitor dostarlimab (Jemperli) for the treatment of adult patients with stage II/III locally advanced rectal cancer that is microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR), as determined by an FDA-authorized test for solid tumors.
Efficacy for dostarlimab in this indication was evaluated in the multicenter, single-arm, open-label AZUR-1 trial (ClinicalTrials.gov identifier NCT05723562) in 154 patients with previously untreated, histologically confirmed, MSI-H/dMMR, stage II/III locally advanced rectal cancer.
AZUR-1 Trial
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 magnetic resonance imaging (MRI), and computed tomography (CT) scans of the chest, abdomen, and pelvis at week 6, 12, and approximately 3 weeks after completing treatment. Patients who achieved a clinical complete response at either of the first two posttreatment assessments entered a non-operative management period, during which they were closely monitored for recurrence through regular multimodal assessments conducted every 4 months for the first 2 years and every 6 months thereafter. Patients who did not experience clinical complete response, or whose disease recurred or progressed, were evaluated for standard-of-care management at investigator discretion.
The primary efficacy outcome measure was sustained clinical complete response for 12 months per independent central review, measured from the first disease assessment after the last administered dose of dostarlimab where clinical complete response was observed. Additional efficacy outcome measures included investigator assessments of sustained clinical complete response for 12 months and objective response rate by both independent central review and investigator review.
Study Results
Of 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; and 4 (2.5%) withdrew or were lost to follow-up.
In 116 patients evaluable for independent central review, the rate of sustained clinical complete response for 12 months was 47% (95% confidence interval [CI] = 27%–56%). In addition, 38 patients (33%) achieved clinical complete response by independent central review who had less than 12 months of follow-up at the time of the data cut-off, and 44 patients (38%) had a near-complete response.
With a median follow-up of 26.3 months, none of the patients with sustained clinical complete response for 12 months, clinical complete response, or near-complete response experienced disease progression.
The objective response rate per independent central review was 79% (95% CI = 71%–85%). In 144 patients evaluable for investigator assessments, the sustained clinical complete response for 12 months rate was 68% (95% CI = 60%–76%) and the objective response rate was 82% (95% CI = 75%–88%). Of the 15 patients who underwent surgery after dostarlimab alone, based on imaging findings suggesting incomplete response, pathological complete response was reported in 12 patients.
Phase II Study of Dostarlimab in Locally Advanced dMMR Solid Tumors
In addition, the FDA reviewed an investigator-led, multicenter, single-arm, open-label trial (ClinicalTrials.gov identifier NCT04165772) that assessed dostarlimab 500 mg intravenously every 3 weeks for nine cycles in 50 patients with previously untreated, MSI-H/dMMR, stage II/III locally advanced rectal cancer.
The sustained clinical complete response for 12 months rate was 93% (95% CI = 82%–99%) and the objective response rate was 100% (95% CI = 93%–100%). No patients received chemoradiation and/or rectal cancer surgery as part of the treatment of locally advanced rectal cancer. Of the 27 patients who have been 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.
Dosage and Safety of Dostarlimab
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 recommended dose for dostarlimab is 500 mg every 3 weeks until disease progression or unacceptable toxicity, for up to nine cycles.
FDA Facilitates Accelerated Review
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that enables concurrent submission and review among international partners. For this review, FDA collaborated with Health Canada (HC), Israel’s Ministry of Health (IMoH), Switzerland’s Swissmedic (SMC), and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA). The application reviews are ongoing at the other regulatory agencies.
This review was also conducted using the Real-Time Oncology Review (RTOR) program, which streamlined data submission prior to the filing of the entire application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 4 months ahead of the FDA goal date.
This application is part of the FDA Commissioner’s National Priority Review Voucher (CNPV) pilot program, which is designed to accelerate the review of products with the potential to address key national priorities.
This application was granted a Priority Review designation, and dostarlimab previously received a Breakthrough Therapy designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
