FDA Approves Dostarlimab for dMMR/MSI-H Locally Advanced Rectal Cancer

The FDA has granted accelerated approval to dostarlimab-gxly (Jemperli) for the treatment of adult patients with stage II or III mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) locally advanced rectal cancer, as determined by an FDA-authorized test.¹

The approval was supported by findings from the phase 2 AZUR-1 trial (NCT05723562), which evaluated dostarlimab monotherapy in patients with previously untreated stage II/III dMMR/MSI-H locally advanced rectal cancer (n = 154).^1,2 Among patients who were evaluable per independent central review (ICR; n = 116) 47% (95% CI, 27%-56%) achieved a sustained clinical complete response at 12 months (cCR12), meeting the primary end point of the trial.¹ Moreover, patients in the trial achieved an overall response rate (ORR) of 79% (95% CI, 71%-85%).

Among investigator-evaluable patients, the cCR12 rate was 68% (95% CI, 60%-76%), and the ORR was 82% (95% CI, 75%-88%).

The FDA also reviewed data from a multicenter, single-arm, open-label phase 2 trial (NCT04165772), which evaluated dostarlimab in the same population as AZUR-1 (n = 50). Patients in the study achieved a cCR12 rate and an ORR of 93% (95% CI, 82%-99%) and 100% (95% CI, 93%-100%), respectively.

“Today, dostarlimab becomes the first and only approved immunotherapy for adults in the US with MSI-H/dMMR locally advanced rectal cancer,” Tony Wood, chief scientific officer for GSK, stated in a news release.³ “For decades, treatment has relied on chemotherapy, radiation, and surgery. This approval offers a new treatment approach and represents an important step toward more personalized care for these patients.”

The approval follows the August 2026 priority review of a supplemental biologics license application for dostarlimab and comes before the set February 2027 Prescription Drug User Fee Act date.⁴

How was the AZUR-1 trial evaluating dostarlimab designed?

Patients enrolled in the multicenter, open-label study were required to be at least 18 years old, have stage II to III disease that was evaluable both radiologically and endoscopically and identified as dMMR or MSI-H through local or central testing, and have an ECOG performance status of 0 or 1.^2,5

The trial excluded patients who had distant metastatic disease, a history of interstitial lung disease, known additional malignancies that had progressed or needed active treatment within the previous 2 years, had received prior radiation therapy, systemic therapy, or surgery for rectal cancer, .

Participants were given dostarlimab monotherapy at 500 mg intravenously once every 3 weeks for 9 cycles.

The primary end point of the trial was cCR12 per ICR.² Key secondary end points included cCR rates at 24 and 36 months and 3-year event-free survival, ORR, and overall survival.

What were the additional data reported to dostarlimab that supported the approval?

Notably, 33% of patients had experienced a cCR per ICR at less then 12 months of follow-up at the time of cutoff in addition to 38% of patients achieving a near CR.¹ At a median follow-up of 26.3 months, all patients who achieved cCR12, cCR, or a near CR demonstrated disease progression. Additionally, 15 patients underwent surgery following dostarlimab monotherapy, imaging suggests 12 of which achieved a incomplete response or pathological complete response.

In the other phase 2 trial, 27 patients were evaluated by investigators for at least 3 years, 1 of which experienced local recurrence that was treated with lymphadenectomy and 2 others either withdrew or experienced death that was unrelated to the disease under study.

“The AZUR-1 results demonstrate the potential for a fundamentally different treatment approach in this biomarker-defined patient population, and today’s approval means MSI-H/dMMR patients can now access a licensed treatment tailored to the biology of their disease,” said Andrea Cercek, MD, section head of Colorectal Cancer and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at Memorial Sloan Kettering Cancer Center in New York, New York, in a news release.

References

1. FDA grants accelerated approval to dostarlimab for locally advanced rectal cancer. FDA. October 19, 2026. Accessed October 19, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dostarlimab-locally-advanced-rectal-cancer?utm_medium=email&utm_source=govdelivery
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. Jemperli (dostarlimab-gxly) approved in US as first and only immunotherapy for adults with MSI-H/dMMR locally advanced rectal cancer. News Release GSK. October 19. 2026. Accessed October 19, 2026. https://us.gsk.com/en-us/media/press-releases/jemperli-dostarlimab-gxly-approved-in-us-as-first-and-only-immunotherapy-for-adults-with-msi-hdmmr-locally-advanced-rectal-cancer/
4. Jemperli (dostarlimab) accepted for priority review by the US FDA for dMMR/MSI-H locally advanced rectal cancer. News release. GSK. August 24, 2026. Accessed October 19, 2026. https://www.gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-accepted-for-priority-review-by-the-us-fda/
5. A study of dostarlimab in untreated dMMR/​MSI-H locally advanced rectal cancer (AZUR-1). ClinicalTrials.gov. Updated May 26, 2026. Accessed October 19, 2026. https://clinicaltrials.gov/study/NCT05723562