Clinical Report: FDA Approves Dostarlimab for Advanced Rectal Cancer

Overview

The FDA granted accelerated approval to dostarlimab-gxly for adults with previously untreated stage II/III locally advanced MSI-H or dMMR rectal cancer. In the single-arm AZUR-1 trial, 47% of 116 evaluable patients had a sustained clinical complete response for at least 12 months; the objective response rate was 79%.

Background

MSI-H and dMMR status identify the rectal cancer population covered by this approval and must be established using an FDA-authorized test for solid tumors. The approval is based primarily on AZUR-1, a multicenter, open-label, single-arm phase 2 trial, without a randomized comparator. Patients achieving a clinical complete response could enter nonoperative management with surveillance rather than proceeding directly to chemoradiation or surgery. The source notes that longer follow-up is needed to establish response durability.

Data Highlights

Key Findings

• The FDA granted accelerated approval for single-agent dostarlimab-gxly in adults with previously untreated stage II/III locally advanced MSI-H or dMMR rectal cancer, as determined by an FDA-authorized test.
• AZUR-1 enrolled 154 patients and assessed response using endoscopy, rectal MRI, and CT imaging; its primary efficacy endpoint was sustained clinical complete response for 12 months by independent central review.
• Among 116 evaluable AZUR-1 patients, 47% achieved sustained cCR for 12 months; a further 38 patients had cCR but less than 12 months of follow-up at data cutoff, and 44 achieved near-complete response.
• The AZUR-1 objective response rate was 79%. At median follow-up of 26.3 months, no progression was observed among patients classified as having sustained cCR, cCR, or near-complete response.
• Of 154 treated patients, 110 (71%) received dostarlimab alone without additional cancer treatment or disease progression; 26 (17%) underwent surgery and 13 (8%) received additional systemic therapy or radiation.
• The prescribing information warns of potentially severe or fatal immune-mediated adverse reactions, infusion-related reactions, complications following allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity; it calls for monitoring liver enzymes, creatinine, and thyroid function.

Clinical Implications

Dostarlimab-gxly is administered at 500 mg intravenously every 3 weeks for up to 9 cycles, until disease progression or unacceptable toxicity. Under the AZUR-1 protocol, patients achieving cCR undergo surveillance every 4 months for the first 2 years and every 6 months thereafter. The source identifies the absence of randomized comparators and the need for longer follow-up to establish durability of response.

Conclusion

Accelerated approval provides a dostarlimab treatment option for adults with previously untreated stage II/III locally advanced MSI-H or dMMR rectal cancer. The reported response findings come primarily from a single-arm trial, and longer follow-up is needed to assess durability.

Related Resources & Content

1. U.S. Food and Drug Administration, FDA, 2026 -- FDA grants accelerated approval to dostarlimab for locally advanced rectal cancer
2. The ASCO Post, 2026 -- FDA Approves Dostarlimab for MSI-H/dMMR Locally Advanced Rectal Cancer
3. U.S. National Library of Medicine, DailyMed, n.d. -- Jemperli (dostarlimab-gxly) prescribing information
4. Cercek et al., New England Journal of Medicine, 2022 -- PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer
5. European Society for Medical Oncology, Annals of Oncology, 2025 -- Localised rectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
6. the asco post — Regular Approval for Dostarlimab-gxly in dMMR Recurrent or Advanced Endometrial Cancer
7. the asco post — FDA Expands Endometrial Cancer Indication for Dostarlimab-gxly With Chemotherapy
8. The ASCO Post — Dostarlimab-gxly for Mismatch Repair–Deficient Recurrent or Advanced Endometrial Cancer
9. FDA grants accelerated approval to dostarlimab for locally advanced rectal cancer
10. FDA Approves Dostarlimab for MSI-H/dMMR Locally Advanced Rectal Cancer
11. Jemperli (dostarlimab-gxly) prescribing information
12. PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer
13. Localised rectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
14. FDA grants accelerated approval to dostarlimab for locally advanced rectal cancer | FDA
15. Localised rectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up☆ - Annals of Oncology
16. PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer | New England Journal of Medicine