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). 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. 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.² “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 announcement of priority review for a supplemental biologics license application for dostarlimab in this indication and comes before the set February 2027 Prescription Drug User Fee Act target action date.³

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 of age and 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.⁴

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

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

Key secondary end points included cCR rates at 24 and 36 months, as well as 3-year event-free survival rate, ORR, and overall survival.⁴

What additional clinical trial data supported the FDA approval of dostarlimab for dMMR/MSI-H rectal cancer?

In AZUR-1, 33% of patients had experienced a cCR per ICR at less than 12 months of follow-up at the time of cutoff, and 38% of patients achieved a near CR.¹ At a median follow-up of 26.3 months, all patients who achieved cCR12, cCR, or near CR had disease progression. Additionally, 15 patients underwent surgery following dostarlimab monotherapy, and imaging suggested that 12 of these patients achieved an incomplete response or pathological CR.

“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,” 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, added in the news release.²

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

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. 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/
3. 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/
4. 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