FDA Approves Dostarlimab for Patients With MSI-H/dMMR Locally Advanced Rectal Cancer

Clinical Summary:

• Regulatory Update: Based on results from the AZUR-1 trial, the FDA has granted accelerated approval to dostarlimab for adults with previously untreated stage II/III MSI-H/dMMR locally advanced rectal cancer. 
• Key Outcomes: In this single-arm study, dostarlimab produced sustained clinical complete responses that allowed many patients to enter nonoperative management, with no disease progression observed among patients achieving complete or near-complete responses at the time of analysis. 
• Clinical Relevance: This approval introduces an immunotherapy-based treatment approach that may allow selected patients with MSI-H/dMMR rectal cancer to avoid chemoradiation and surgery.

Based on results from the AZUR-1 trial, the US Food and Drug Administration (FDA) granted accelerated approval to dostarlimab (Jemperli; GSK) for the treatment of patients with stage II/III locally advanced rectal cancer that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), introducing an immunotherapy-based treatment approach that may allow selected patients to avoid surgery and other conventional treatments.

In this open-label, single-arm trial, 154 patients with histologically confirmed stage II/III MSI-H/dMMR locally advanced rectal cancer who had not received prior treatment received 500 mg of dostarlimab intravenously every 3 weeks for 9 cycles or until disease progression or unacceptable toxicity. 

Treatment response was evaluated using endoscopy, rectal magnetic resonance imaging (MRI), and computed tomography (CT) of the chest, abdomen, and pelvis at weeks 6 and 12 and approximately 3 weeks after treatment completion.

Patients who achieved a clinical complete response at either of the first 2 post-treatment assessments entered a nonoperative management period, with surveillance every 4 months during the first 2 years and every 6 months thereafter.

Patients without a clinical complete response, or those who experienced disease recurrence or progression, were evaluated for additional standard treatment at investigator discretion.

The primary efficacy end point was sustained clinical complete response for at least 12 months, assessed by independent central review. Additional end points included investigator-assessed clinical complete response for at least 12 months and objective response rate (ORR) by both independent and investigator assessments.

Among the 154 patients treated in AZUR-1, 110 (71%) received dostarlimab without subsequent surgery, systemic therapy, or radiation and had not experienced disease progression at the data cutoff. An additional 26 patients (17%) underwent surgery, with or without additional systemic treatment or radiation, while 13 patients (8%) received additional systemic therapy or radiation without surgery. One patient experienced disease progression without further treatment, and 4 patients withdrew or were lost to follow-up.

Among 116 patients evaluable by independent central review, the 12-month clinical complete response rate was 47%. An additional 38 patients (33%) had achieved a clinical complete response but had less than 12 months of follow-up at the data cutoff. Near-complete responses were documented in 44 patients (38%).

At a median follow-up of 26.3 months, no disease progression was reported among patients classified as having clinical complete response for at least 12 months, clinical complete response, or near-complete response.The ORR was 79%.

Among 144 patients evaluable by investigators, the 12-month clinical complete response rate was 68%, and the ORR was 82%.

Notably, among 15 patients who underwent surgery following dostarlimab monotherapy because imaging suggested an incomplete response, 12 were found to have a pathological complete response.

The recommended dose is 500 mg of dostarlimab intravenously every 3 weeks for up to 9 cycles or until disease progression or unacceptable toxicity.

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

Source:

US Food and Drug Administration. FDA grants accelerated approval to dostarlimab for locally advanced rectal cancer. Accessed on: October 19, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dostarlimab-locally-advanced-rectal-cancer