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19th Oct, 2026 12:00 AM

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FDA Approves Dostarlimab for Rectal Cancer

The FDA has granted accelerated approval to dostarlimab (Jemperli, GSK) for rectal cancer indications.

The drug is now approved for adults with stage II/III locally advanced rectal cancer (LARC) that is microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR).

The PD-1 inhibitor is the first immunotherapy to be approved specifically for MSI-H or dMMR rectal cancer, which accounts for 5%-10% of tumors. Based on the results of the approval study, AZUR-1, GSK said dostarlimab could help eligible patients avoid chemotherapy, radiation, and surgery.

Dostarlimab carries previous approvals for endometrial cancer and dMMR recurrent or advanced solid tumors. A patient's eligibility for the drug's new rectal cancer indications needs to be determined by an FDA-authorized test.

Article Key Points

FDA accelerated approval: dostarlimab for stage II/III MSI-H or dMMR LARC.
First immunotherapy approved specifically for MSI-H/dMMR rectal cancer.
AZUR-1: cCR12 47% central review; ORR 79%; no recurrences in responders >2 yrs.
Surgery subset: 12/15 had pathologic complete response after monotherapy.
AEs: fatigue 32%, rash 22%, diarrhea 18%; 3% discontinued, 20% serious AEs.

Dive Deeper

What biomarkers predict response in MSI-H rectal cancer?

How does dostarlimab compare with standard chemoradiation?

What long-term outcomes follow nonoperative rectal cancer management?

AZUR-1 was a single-arm study of 154 previously untreated MSI-H or dMMR LARC patients treated with 500 mg dostarlimab intravenously every 3 weeks for up to nine cycles.

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Clinical complete response at 12 months (cCR12) by independent central review, the primary outcome, was 47% (54/116 evaluable patients). In addition, 38 patients (33%) who had been followed less than 12 months at data cutoff had a cCR. The objective response rate (ORR) was 79%. Sixty-eight percent of evaluable patients (98/144) achieved a cCR12 by investigator analysis, with an ORR of 82%. No disease recurrences have been reported among responders after a median follow-up of more than 2 years. Of 15 patients who underwent surgery after dostarlimab monotherapy, 12 were found to have had a pathologic complete response.

The FDA also reviewed a single-arm, open-label trial in 50 patients with previously untreated disease. The cCR12 rate was 93% and ORR was 100%; none of the patients received chemoradiation and/or surgery as part of treatment. Of the 27 patients followed at least 3 years, only one had a local recurrence, which was treated with lymphadenectomy.

The most common adverse reactions in AZUR-1 were fatigue (32%), rash (22%), diarrhea (18%), and pruritus (17%), with 3% of patients discontinuing due to adverse events. Twenty percent of patients had serious adverse reactions.

Labeling contains warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

The recommended dostarlimab dose is the same as in the studies, 500 mg every 3 weeks for up to nine cycles.

The approval was made under the FDA's National Priority Review Voucher pilot program. Continued approval for the indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s), GSK noted.

M. Alexander Otto is a physician assistant and award-winning journalist. He is also an MIT science journalism fellow. Email: aotto@medscape.net

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Commonly Asked by HCPs

Q: What testing is recommended to identify MSI-H or dMMR status in colorectal tumors?

A: MSI-H and dMMR status are generally determined with validated tumor testing, commonly immunohistochemistry for mismatch repair proteins and/or molecular assays for microsatellite instability. These biomarkers are important in colorectal cancer because they identify patients more likely to benefit from immune checkpoint inhibitors and may influence treatment planning across localized and advanced disease settings.

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Q: What immune-related toxicities should clinicians monitor during PD-1 inhibitor therapy?

A: PD-1 inhibitors can cause immune-mediated adverse effects involving the skin, gastrointestinal tract, endocrine organs, liver, lungs, and other systems. Clinicians generally monitor for fatigue, rash, diarrhea, pruritus, and more serious toxicities, with attention to early recognition, treatment interruption when needed, and evaluation for infusion reactions or other rare but clinically significant complications.

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Q: How is locally advanced rectal cancer typically managed in patients with MSI-H or dMMR tumors?

A: Management of locally advanced rectal cancer usually combines staging, multimodality therapy, and careful selection for surgery, radiation, and systemic treatment. In MSI-H or dMMR disease, immunotherapy has become an important option because these tumors can be highly responsive, potentially allowing some patients to avoid conventional chemoradiation and surgery while still requiring close oncologic follow-up.

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Q: When should immunotherapy be considered instead of chemoradiation or surgery for rectal cancer?

A: Immunotherapy is most relevant in rectal cancer when the tumor is MSI-H or dMMR and the disease is locally advanced but potentially curable. Research typically focuses on whether checkpoint blockade can induce deep clinical responses that permit nonoperative management, while balancing the need for definitive local control and the uncertainty of long-term durability in selected patients.

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Q: What are the long-term outcomes and surveillance needs after organ-preserving treatment of rectal cancer?

A: After organ-preserving treatment for rectal cancer, long-term care centers on surveillance for local recurrence, distant relapse, and functional outcomes. Follow-up typically includes serial clinical assessment, endoscopic evaluation, imaging when indicated, and multidisciplinary review, because durable complete responses can occur but recurrence risk and the optimal duration of nonoperative surveillance remain important areas of study.

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