Dostarlimab Achieves Sustained Clinical Complete Responses in dMMR/MSI-H Rectal Cancer

Dostarlimab-gxly (Jemperli) monotherapy produced a sustained clinical complete response at 12 months (cCR12) that met the primary end point of the phase 2 AZUR-1 trial (NCT05723562) in patients with stage II/III mismatch repair–deficient/microsatellite instability-high (dMMR/MSI-H) locally advanced rectal cancer.¹

Data from the interim analysis of the single-arm, registrational trial showed a cCR12 rate that investigators described as clinically meaningful and durable, representing a substantial improvement over the historical standard of care. In a news release, GSK stated that the findings support the potential for dostarlimab, if approved, to become the first immunotherapy able to eliminate or delay the need for chemotherapy, radiation, and surgery for some patients in this population.

“The AZUR-1 results support the potential for dostarlimab to transform treatment for dMMR/MSI-H locally advanced rectal cancer,” Hesham Abdullah, senior vice president, global head oncology, R&D at GSK, stated in the news release. “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 was AZUR-1 designed?

AZUR-1 is a global, multicenter, open-label, nonrandomized, single-arm registrational phase 2 trial evaluating dostarlimab monotherapy in patients with previously untreated stage II/III dMMR/MSI-H locally advanced rectal cancer.¹^,² The trial enrolled 154 participants, who received dostarlimab at 500 mg intravenously every 3 weeks for 9 cycles over 6 months. The primary objective was to assess whether sustained cCR12 could be achieved with dostarlimab alone, without chemotherapy, radiation, or surgery.

What earlier data supported the AZUR-1 trial?

AZUR-1 builds on earlier investigator-led research, which first demonstrated that dostarlimab monotherapy could produce clinical complete responses without chemotherapy, radiation, or surgery in dMMR locally advanced rectal cancer.¹ Updated findings from that phase 2 study (NCT04165772), reported this year, showed that all 42 patients who completed treatment achieved a clinical complete response, with 24 patients reaching sustained cCR12 at a median follow-up of 26.3 months (range, 12.4-50.5).³

Rectal cancer affects an estimated 730,000 people globally each year, and approximately 5% to 10% of rectal cancers carry the dMMR/MSI-H subtype.¹

What is the safety profile and regulatory path forward for dostarlimab?

In the interim analysis, the safety and tolerability profile of dostarlimab was consistent with its well-characterized and manageable safety profile previously observed across solid tumors.¹

Dostarlimab has received both breakthrough therapy and fast track designations from the FDA in this setting. GSK stated it plans to share the interim AZUR-1 data with global regulatory authorities, including for accelerated review in the United States.

References

1. Jemperli (dostarlimab) achieves sustained clinical complete responses in dMMR/MSI-H locally advanced rectal cancer. News release. GSK. July 13, 2026. Accessed July 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 JB, Capdevila J, et al. A phase two, single-arm, open-label study with dostarlimab monotherapy in participants with untreated stage II/III dMMR/MSI-H locally advanced rectal cancer (AZUR-1). Clin Colorectal Cancer. 2025;24(2):325-330. doi:10.1016/j.clcc.2025.02.003
3. Seymour C. Dostarlimab 2 for 2: Snagging 100% Clinical CR in dMMR Locally Advanced Rectal Cancer. OncLive. Published June 8, 2026. Accessed July 13, 2026. https://www.onclive.com/view/dostarlimab-2-for-2-snagging-100-clinical-cr-in-dmmr-locally-advanced-rectal-cancer