The US FDA has accepted for priority review a supplemental Biologics License Application (sBLA) for dostarlimab (Jemperli), GSK's (LSE/NYSE: GSK) PD-1-blocking monoclonal antibody, for the treatment of previously untreated stage II and III mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer. The FDA set a PDUFA date in February 2027. The application is also eligible for expedited review through the National Priority Voucher program.
The sBLA is supported by data from AZUR-1, a global, open-label, single-arm, registrational Phase II trial enrolling 154 patients with previously untreated stage II and III dMMR/MSI-H locally advanced rectal cancer. The trial's primary endpoint was a sustained clinical complete response at 12 months (cCR12). In interim data, GSK reported the cCR12 rate was clinically meaningful and durable, representing a substantial improvement over the historical standard of care, according to the company. Full numerical data have not yet been disclosed publicly and are expected to be presented at a scientific congress later in 2026. The safety profile was described as consistent with dostarlimab's established profile across solid tumors. The AZUR-1 findings build on earlier work from Memorial Sloan Kettering Cancer Center (MSK), where a Phase II study in 42 evaluable patients with dMMR locally advanced rectal cancer reported a 100% clinical complete response rate, with a median follow-up of 17.9 months and no patient requiring chemotherapy, radiation, or surgery.
Rectal cancer affects approximately 770,000 people globally each year, with dMMR/MSI-H tumors accounting for roughly 5–10% of cases. Current standard of care — neoadjuvant chemotherapy, radiation, and surgery — can carry lasting effects on bowel, urinary, and sexual function. If approved, dostarlimab would become the first immunotherapy indicated for this setting, potentially allowing some patients to forgo all three conventional treatment modalities.
Dostarlimab previously received Fast Track and Breakthrough Therapy Designation for this indication, the latter granted in December 2024. The drug carries multiple existing FDA approvals in endometrial cancer, including a tumor-agnostic accelerated approval for dMMR solid tumors granted in August 2021. The closest approved immunotherapy comparator in dMMR colorectal cancers involves Bristol Myers Squibb's nivolumab (Opdivo) plus ipilimumab (Yervoy), which received FDA approval in April 2025 for unresectable or metastatic dMMR/MSI-H colorectal cancer — a distinct, later-stage population from the locally advanced rectal cancer setting targeted by the AZUR-1 program.
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