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

Dostarlimab (Jemperli) monotherapy produced a clinically meaningful and sustained clinical complete response (cCR) rate at 12 months in patients with stage II/III mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer, according to interim results from the registrational phase 2 AZUR-1 trial (NCT05723562) shared in a news release from developer GSK.¹ The single-arm trial met its primary objective in this interim analysis, and the company plans to share the data with global regulatory authorities, including for potential accelerated review in the US.

What were the key findings from the AZUR-1 interim analysis?

The trial’s primary objective, sustained cCR at 12 months was met, supporting the potential for dostarlimab, if approved, to become the first immunotherapy capable of eliminating or delaying the need for chemotherapy, radiation, and surgery for some patients with dMMR/MSI-H locally advanced rectal cancer. The safety and tolerability profile observed in the interim analysis was consistent with dostarlimab’s well-characterized profile across solid tumors.

Detailed results, including secondary end points, are expected to be presented at a future scientific congress.

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

Why does this treatment approach matter for patients with rectal cancer?

Standard of care for locally advanced disease typically includes chemotherapy, radiation, and surgery, which can profoundly affect quality of life, potentially leading to lifelong colostomy use, significant physiologic dysfunction, and infertility.

The AZUR-1 results build on earlier research conducted in collaboration with Memorial Sloan Kettering Cancer Center, which first demonstrated that dostarlimab could achieve cCRs without chemotherapy, radiation, or surgery in patients with dMMR/MSI-H locally advanced rectal cancer.² CancerNetwork® previously covered updated data from that cohort, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, in which all 42 patients who completed treatment had a clinical complete response, with 24 patients experiencing a cCR sustained to 12 months.³

What is the AZUR-1 trial design?

AZUR-1 is a global, open-label, single-arm, registrational phase 2 trial evaluating dostarlimab monotherapy in patients with stage II/III dMMR/MSI-H locally advanced rectal cancer. The trial enrolled 154 participants, who received 9 cycles of dostarlimab over 6 months, administered as a 500 mg intravenous infusion every 3 weeks.⁴ Patients were excluded if they had distant metastatic disease, receipt of prior radiation therapy, systemic therapy, or surgery for rectal cancer, and any history of interstitial lung disease or pneumonitis.

The primary end point of the study was the sustained cCR rate at 12 months, assessed by independent central review, to determine whether dostarlimab alone could allow patients to avoid chemotherapy, radiation, and/or surgery. Secondary end points included the sustained cCR rates at 24 and 36 months, as well as event-free survival, objective response rate, and overall survival.

What is dostarlimab's regulatory history in rectal cancer?

Dostarlimab has received both breakthrough therapy and fast track designations from the FDA for dMMR/MSI-H locally advanced rectal cancer. CancerNetwork previously covered the breakthrough therapy designation, granted in December 2024 based on the 100% cCR rate observed in the earlier MSK-collaborative cohort.⁵ Dostarlimab is not currently approved anywhere in the world for rectal cancer. GSK plans to share the AZUR-1 interim data with global regulatory authorities, including for potential accelerated review in the US.

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://tinyurl.com/54av3v7m
2. Cercek A, Roxburgh CSD, Strombom P, et al. Adoption of total neoadjuvant therapy for locally advanced rectal cancer. JAMA Oncol. 2018;4(6):e180071. doi:10.1001/jamaoncol.2018.0071
3. Cercek A, Sinopoli JC, Shia J, et al. Durable complete responses to PD-1 blockade alone in mismatch repair deficient locally advanced rectal cancer. J Clin Oncol. 2024;42(suppl 17):LBA3512. doi:10.1200/JCO.2024.42.17_suppl.LBA3512
4. A study of dostarlimab in untreated dMMR/MSI-H locally advanced rectal cancer (AZUR-1). ClinicalTrials.gov. Updated May 26, 2026. Accessed July 13, 2026. https://tinyurl.com/4nze7wnf
5. Jemperli (dostarlimab-gxly) receives US FDA breakthrough therapy designation for locally advanced dMMR/MSI-H rectal cancer. News release. GSK. December 16, 2024. Accessed July 13, 2026. https://tinyurl.com/2nkurvce