On October 19, 2026, the US Food and Drug Administration (FDA) 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.
What Was Behind the FDA Approval?
The FDA’s decision was supported by efficacy results from AZUR-1 (NCT05723562), a multicenter, single-arm, open-label trial evaluating dostarlimab in patients with previously untreated MSI-H/dMMR locally advanced rectal cancer. Additional supporting evidence came from an investigator-led, multicenter, single-arm study (NCT04165772) involving 50 patients with the same disease characteristics.
AZUR-1 enrolled 154 patients with previously untreated, histologically confirmed stage II/III MSI-H/dMMR locally advanced rectal cancer. Patients received dostarlimab 500 mg intravenously every three weeks for nine cycles, unless unacceptable toxicity or disease progression occurred.
Tumor response was evaluated using endoscopy, rectal MRI, and CT imaging of the chest, abdomen, and pelvis at weeks 6 and 12, and approximately three weeks after treatment completion. Patients who achieved a clinical complete response (cCR) at either of the first two post-treatment assessments entered a non-operative management period, with surveillance every four months during the first two years and every six months thereafter.
Patients who did not achieve cCR, or whose disease recurred or progressed, were evaluated for standard-of-care management at the investigator’s discretion. The primary efficacy endpoint was sustained clinical complete response for 12 months (cCR12), assessed by independent central review (ICR). Additional endpoints included investigator-assessed cCR12 and objective response rate (ORR).
Key Findings
Among the 154 patients treated in AZUR-1:
- 110 patients (71%) received dostarlimab alone, did not receive additional treatment, and did not experience disease progression.
- 26 patients (17%) underwent surgery, with or without additional systemic therapy or radiation.
- 13 patients (8%) received additional systemic therapy or radiation.
- One patient (0.6%) experienced disease progression without further treatment.
- Four patients (2.5%) withdrew or were lost to follow-up.
Among 116 patients evaluable by independent central review, the cCR12 rate was 47%. An additional 38 patients (33%) had achieved cCR but had less than 12 months of follow-up at the time of the data cutoff, while 44 patients (38%) had a near-complete response.
The ORR by independent central review was 79% (95% CI, 71%–85%). Among 144 investigator-evaluable patients, the cCR12 rate was 68% (95% CI, 60%–76%), and the ORR was 82% (95% CI, 75%–88%). At a median follow-up of 26.3 months, no disease progression was reported among patients who had achieved cCR12, cCR, or near-complete response. Among 15 patients who underwent surgery after dostarlimab alone because imaging suggested an incomplete response, 12 had a pathological complete response.
Supporting Evidence From an Investigator-Led Study
The FDA also reviewed results from NCT04165772, an investigator-led, multicenter, single-arm, open-label study involving 50 patients with previously untreated stage II/III MSI-H/dMMR locally advanced rectal cancer. Patients received dostarlimab 500 mg intravenously every three weeks for nine cycles.
The study reported:
- cCR12 rate: 93% (95% CI, 82%–99%).
- Objective response rate: 100% (95% CI, 93%–100%).
No patients received chemoradiation or rectal cancer surgery as part of their treatment for locally advanced rectal cancer. Among 27 patients followed for at least three years, one experienced a local recurrence that was treated with lymphadenectomy, one withdrew from the study, and one died from causes unrelated to the disease under investigation. These results provided additional supporting evidence for dostarlimab in this molecularly defined patient population.
Safety and Recommended Dosing
The recommended dose of dostarlimab is 500 mg intravenously every three weeks for up to nine cycles, until disease progression or unacceptable toxicity. The prescribing information includes warnings and precautions regarding immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.
Regulatory Review and International Collaboration
The FDA reviewed the application under Project Orbis, an initiative of the FDA Oncology Center of Excellence that facilitates concurrent regulatory review of oncology treatments among participating countries.
The FDA collaborated with Health Canada, Israel’s Ministry of Health, Swissmedic, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency. Reviews by these regulatory authorities were ongoing at the time of the announcement. The application was also reviewed through the Real-Time Oncology Review program, with the use of the Assessment Aid, and was included in the FDA Commissioner’s National Priority Review Voucher pilot program.
The application received priority review, and dostarlimab was granted breakthrough therapy designation. The FDA completed its review four months ahead of the agency’s goal date.
Conclusion
The FDA’s accelerated approval of dostarlimab provides a treatment option for adults with stage II/III MSI-H/dMMR locally advanced rectal cancer. In AZUR-1, 110 of 154 treated patients (71%) received dostarlimab alone, did not receive additional treatment, and did not experience disease progression. The sustained clinical complete response rate at 12 months (cCR12) was 47% by independent central review among 116 evaluable patients. In the supporting investigator-led study involving 50 patients, the cCR12 rate was 93%. These results formed the clinical evidence supporting the FDA’s accelerated approval of dostarlimab in this patient population.
The full announcement is available on the official FDA website.
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