The FDA has accepted for priority review a supplemental biologics license application (sBLA) for dostarlimab-gxly (Jemperli) in patients with previously untreated stage II and III mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer, according to a news release from developer GSK.1 The agency has assigned a Prescription Drug User Fee Act (PDUFA) action date of February 2027, and the application is also eligible for expedited review through the National Priority Voucher program.
The application was accepted under Project Orbis, an FDA Oncology Center of Excellence initiative that enables coordinated reviews by international health authorities and may support earlier regulatory decisions and patient access.
What data support the priority review application?
The sBLA is supported by data from the registrational phase 2, single-arm AZUR-1 trial (NCT05723562), which demonstrated a meaningful and sustained clinical complete response rate at 12 months (cCR12), with no detectable signs of cancer for at least 1 year. The safety and tolerability profile of dostarlimab was generally consistent with its established profile across solid tumors in interim data as well.2 Full results, including secondary end points, are expected to be presented at a scientific congress later in 2026.
According to the developers, the AZUR-1 results represent a substantial improvement compared with the historical standard of care. The data support the potential for dostarlimab, if approved, to become the first immunotherapy capable of eliminating or delaying the need for chemotherapy, radiation, and surgery for some patients in this population. These findings build on earlier research conducted with Memorial Sloan Kettering Cancer Center, which showed the potential for dostarlimab to achieve clinical complete responses without other treatment in patients with dMMR/MSI-H locally advanced rectal cancer.
What is the AZUR-1 trial design?
AZUR-1 is a global, open-label, single-arm, registrational phase 2 trial evaluating dostarlimab monotherapy in patients with previously untreated stage II and III dMMR/MSI-H locally advanced rectal cancer (n = 154).3 Patients received 9 cycles of dostarlimab over 6 months, administered as a 500-mg intravenous infusion every 3 weeks. The trial was designed to assess sustained cCR12 and determine whether dostarlimab alone could enable patients to avoid chemotherapy, radiation, and surgery.
Eligible patients in the trial had histologically confirmed stage II to III, locally advanced rectal cancer which can be categorized as dMMR or MSI-H by local or central assessment and is radiologically and endoscopically evaluable.3 Exclusion criteria included distant metastatic disease, prior receipt of radiation therapy, systemic therapy, or surgery, and history of interstitial lung disease or pneumonitis.
The primary end point was the number of patients with cCR12 as assessed by independent central review. Secondary end points included number of participants with sustained complete clinical response for 24 months, number of participants with sustained complete clinical response for 36 months, event-free survival, objective response rate, organ preservation rate, overall survival, and safety.
What is dostarlimab’s regulatory history in rectal cancer?
Dostarlimab was previously granted fast track and breakthrough therapy designations by the FDA in this setting.4 Dostarlimab was granted breakthrough therapy designation in this setting in December 2024, based on earlier cCR data from the MSK-collaborative cohort. Dostarlimab is not currently approved anywhere globally for locally advanced rectal cancer.
References
- 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 August 24, 2026. https://tinyurl.com/2p9nwv9z
- Jemperli (dostarlimab) achieves sustained clinical complete responses in dMMR/MSI-H locally advanced rectal cancer. News release. GSK. July 13, 2026. Accessed August 24, 2026. https://tinyurl.com/54av3v7m
- A study of dostarlimab in untreated dMMR/MSI-H locally advanced rectal cancer (AZUR-1). ClinicalTrials.gov. Updated May 26, 2026. Accessed August 24, 2026. https://tinyurl.com/4nze7wnf
- Jemperli (dostarlimab-gxly) receives US FDA breakthrough therapy designation for locally advanced dMMR/MSI-H rectal cancer. News release. GSK. December 16, 2024. Accessed August 24, 2026. https://tinyurl.com/3arxmak3
