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

The FDA has granted accelerated approval to dostarlimab (Jemperli) for adults with stage II or III locally advanced rectal cancer (LARC) that is microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR), offering a treatment option that may allow patients to avoid surgery, radiation, and additional systemic therapy.¹

The approval, granted after a priority review of a supplemental biologics license application, was supported by results from the phase 2 AZUR-1 trial (NCT05723562), in which dostarlimab demonstrated antitumor activity in previously untreated patients with MSI-H/dMMR LARC. Among patients evaluated by independent central review (ICR), the objective response rate (ORR) was 79%, and 47% achieved a sustained clinical complete response lasting at least 12 months (cCR12).

About AZUR-1

AZUR-1 was a multicenter, single-arm, open-label trial involving 154 patients with previously untreated stage II or III MSI-H/dMMR LARC.² Patients received dostarlimab 500 mg intravenously every 3 weeks for 9 cycles, unless they experienced unacceptable toxicity or disease progression.

At a median follow-up of 26.3 months, 110 of 154 patients (71%) had received dostarlimab alone, required no additional treatment, and experienced no disease progression. Another 26 patients (17%) underwent surgery, with or without additional systemic therapy or radiation, and 13 (8%) received additional systemic therapy or radiation. One patient experienced disease progression without further treatment, and 4 withdrew or were lost to follow-up.

Among 15 patients who underwent surgery after dostarlimab because imaging suggested an incomplete response, 12 achieved a pathological complete response. At the data cutoff, 38 additional patients had achieved a clinical complete response but had less than 12 months of follow-up, while 44 had achieved a near-complete response. No disease progression had occurred among patients with a clinical complete response, near-complete response, or sustained clinical complete response.

Additional Supporting Evidence and Safety

The FDA also reviewed an investigator-led, multicenter, single-arm, open-label trial (NCT04165772) involving 50 previously untreated patients with stage II or III MSI-H/dMMR LARC who received the same dostarlimab regimen. The cCR12 rate was 93% (95% CI, 82%-99%), and the ORR was 100% (95% CI, 93%-100%). No patients received chemoradiation or rectal cancer surgery as part of their LARC treatment.

The recommended dostarlimab dose is 500 mg intravenously every 3 weeks for up to 9 cycles, until disease progression or unacceptable toxicity. The prescribing information includes warnings for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

REFERENCES

1. FDA grants accelerated approval to dostarlimab for locally advanced rectal cancer. News release. US FDA. October 19, 2026. Accessed October 19, 2026. https://tinyurl.com/2zkmyehy

2. 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