The U.S. Food and Drug Administration (FDA) has accepted for Priority Review GSK’s supplemental Biologics License Application (sBLA) for Jemperli (dostarlimab) for patients with previously untreated stage II and III mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer.
The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date in February 2027. The application is also eligible for expedited review through the National Priority Voucher program, which could potentially result in an earlier FDA decision.
The application has also been accepted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that enables coordinated review of oncology products by international regulatory authorities.
Rectal cancer affects approximately 770,000 people worldwide each year, and around 5–10% of cases are characterized by dMMR/MSI-H.
For patients with locally advanced rectal cancer, treatment commonly involves chemotherapy, radiation and surgery. Although these approaches can be effective, they may also have lasting effects on bowel, urinary and sexual function, fertility and overall quality of life.
If approved for this indication, dostarlimab could provide some patients with dMMR/MSI-H locally advanced rectal cancer with an opportunity to avoid or delay chemotherapy, radiation and surgery.
AZUR-1 Trial of Jemperli in Rectal Cancer
The regulatory application is supported by positive interim results from the Phase II AZUR-1 trial (NCT05723562).
AZUR-1 is a global, open-label, single-arm registrational study evaluating dostarlimab monotherapy in patients with previously untreated stage II/III dMMR/MSI-H locally advanced rectal cancer.
The trial enrolled 154 participants. Patients receive dostarlimab, a PD-1-blocking antibody, and those who achieve a clinical complete response can enter non-operative management with close surveillance rather than proceeding immediately to chemotherapy, radiation, or surgery.
The study met its primary objective, demonstrating a meaningful and sustained clinical complete response rate at 12 months. This means that a significant proportion of participants had no clinically detectable signs of cancer for at least one year after treatment.
The numerical efficacy results from the registrational AZUR-1 study have not yet been publicly disclosed. GSK plans to present the detailed findings at a scientific congress later in 2026.
According to GSK, the safety and tolerability profile observed in the interim analysis was generally consistent with the established and manageable safety profile of dostarlimab across solid tumors.
The study is also evaluating sustained clinical complete responses at 24 and 36 months, three-year event-free survival, organ preservation, overall survival and additional efficacy and safety outcomes.
Building on Earlier Dostarlimab Research
The AZUR-1 program builds on earlier research conducted with Memorial Sloan Kettering Cancer Center (MSK), which demonstrated the potential of dostarlimab to produce clinical complete responses in patients with dMMR locally advanced rectal cancer without the use of chemotherapy, radiation or surgery.
The registrational AZUR-1 study was subsequently designed to evaluate this treatment strategy in a larger, international patient population.
Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody. The drug previously received FDA Breakthrough Therapy and Fast Track Designations for locally advanced dMMR/MSI-H rectal cancer.
Jemperli is not currently approved for locally advanced rectal cancer, making the Priority Review an important regulatory step toward a potential new indication.
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