Can Dostarlimab Replace Surgery for dMMR/MSI-H Rectal Cancer?

On July 13, GSK announced that the trial for Dostarlimab, AZUR-1, met its primary objective in patients with stage II/III mismatch repair deficient or microsatellite instability-high locally advanced rectal cancer, showing a clinically meaningful and sustained complete response rate at 12 months.¹ Interim results from a registrational phase II trial suggest that the immunotherapy drug alone may allow some patients with a specific subtype of locally advanced rectal cancer to avoid chemotherapy, radiation, and surgery entirely.

The trial enrolled 154 participants who received dostarlimab monotherapy, administered as a 500 mg intravenous infusion every three weeks for nine cycles over six months.¹ Investigators tracked whether patients achieved a sustained clinical complete response, meaning no detectable signs of cancer, for at least a year following treatment. According to GSK, the safety and tolerability profile observed in the interim data was consistent with the drug's established profile across other solid tumors.

Why Does This Matter for Treatment Protocols?

Rectal cancer affects roughly 730,000 people globally each year, and this molecular subtype accounts for an estimated 5% to 10% of cases.¹ Current standard of care for locally advanced disease typically combines chemotherapy, radiation, and surgery. These interventions can be effective, but they carry lasting consequences. A treatment approach that could reduce or eliminate reliance on some or all these interventions would represent a meaningful shift in how this cancer subtype is managed.

The results reinforce a broader trend toward biomarker-driven immunotherapy replacing multimodal standard-of-care regimens in specific patient populations.¹ Mismatch repair deficiency and microsatellite instability create a distinct biological vulnerability: affected tumors accumulate mutations because they cannot properly repair DNA damage, making them more responsive to immune checkpoint inhibitors. That mechanistic rationale also underlies use of this drug class in colorectal, endometrial, and other gastrointestinal cancers, and it is increasingly shaping how sponsors design trials and how manufacturers plan capacity for antibody production.

What Happens Next in the Regulatory Process?

GSK said it plans to share the interim data with global regulatory authorities to support review, including through an accelerated pathway in the US, where the drug already holds Breakthrough Therapy and Fast Track designations for this indication.¹ Detailed results are expected at a future scientific congress. The drug is not currently approved anywhere in the world for rectal cancer.

The results build on earlier research conducted with Memorial Sloan Kettering Cancer Center, which first demonstrated that this checkpoint inhibitor could produce clinical complete responses without additional treatment in this patient population.¹ AZUR-1 was designed to test that finding in a larger, registrational setting and to determine whether monotherapy alone could reliably enable patients to avoid chemotherapy, radiation, or surgery.

Hesham Abdullah, Senior Vice President and Global Head of Oncology, Research and Development, GSK, said in a press release, "The AZUR-1 results support the potential for dostarlimab to transform treatment for dMMR/MSI-H locally advanced rectal cancer. For many patients today, rectal cancer treatment comes with the tolerability burden and lasting impacts from chemotherapy, radiation and surgery. These data demonstrate that some patients may be able to avoid those interventions while remaining free of detectable signs of cancer."

How Is AZUR-1 Standardizing Response Assessment Across Trial Sites?

A newly published trial-design paper in Clinical Colorectal Cancer details how AZUR-1 addresses a longstanding comparability problem across locally advanced rectal cancer studies: inconsistent response criteria.² The trial applies a standardized clinical response schema, adapted from Memorial Sloan Kettering's regression criteria, combining MRI, endoscopy, and pathology findings, with independent central imaging review layered onto investigator assessment. Investigators are also collecting biomarker data, including PD-L1 expression, tumor mutational burden, and circulating tumor DNA dynamics, alongside patient-reported outcomes. That standardization may matter as much as the clinical results, given how fragmented trial designs have complicated cross-study comparisons in this population.

References

1. GSK. Jemperli (dostarlimab) trial continues to show unprecedented results with no evidence of disease in 100% of patients with locally advanced mismatch repair deficient (dMMR) rectal cancer. Press Release. June 13, 2026. https://www.gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-achieves-sustained-clinical-complete-responses-in-dmmrmsi-h-locally-advanced-rectal-cancer/
2. Cercek A, Bachet J-B, Capdevila J, et al. A phase 2, single-arm, open-label study with dostarlimab monotherapy in participants with untreated stage IIIII dMMR/MSI-H locally advanced rectal cancer: AZUR-1. Clinical Colorectal Cancer. 2025;24(2):325-330. doi:10.1016/j.clcc.2025.02.003.