FDA Grants Priority Review to Dostarlimab for dMMR/MSI-H Locally Advanced Rectal Cancer

The FDA has accepted a supplemental biologics license application (sBLA) for dostarlimab (Jemperli; GSK) for priority review in patients with previously untreated stage 2 or 3 mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer. If approved, dostarlimab could become the first immunotherapy indicated in this setting with the potential to eliminate or delay the need for chemotherapy, radiation, and surgery in some patients.¹

The FDA assigned the application a Prescription Drug User Fee Act (PDUFA) action date for February 2027. The submission was also accepted under Project Orbis, an FDA Oncology Center of Excellence initiative that allows concurrent review of oncology therapies by international regulatory authorities. The application is eligible for expedited consideration through the FDA’s National Priority Voucher program.¹

Dostarlimab, a programmed cell death receptor-1 (PD-1) blocking antibody, is not currently approved for locally advanced rectal cancer.

AZUR-1 Supports Potential Organ-Preserving Approach

The sBLA is supported by interim findings from the global, open-label, single-arm phase 2 AZUR-1 trial (NCT05723562), which evaluated dostarlimab monotherapy in 154 patients with previously untreated stage 2 or 3 dMMR/MSI-H locally advanced rectal cancer.¹

The patients received 9 cycles of intravenous dostarlimab over 6 months at a dose of 500 mg every 3 weeks. The study was designed to evaluate the rate of sustained clinical complete response for at least 12 months and determine whether treatment with dostarlimab alone could allow patients to avoid conventional multimodal therapy.¹

The trial met its primary objective, with a clinically meaningful proportion of participants achieving a sustained clinical complete response lasting at least 1 year. A clinical complete response indicates that no detectable evidence of cancer can be identified through clinical evaluation following treatment. Detailed AZUR-1 findings are expected to be presented at a scientific congress later in 2026.¹

The safety and tolerability findings reported in the interim analysis were generally consistent with the established safety profile of dostarlimab across solid tumors.¹

The results build on earlier work from Memorial Sloan Kettering Cancer Center evaluating PD-1 blockade in patients with dMMR locally advanced rectal cancer. In an initial phase 2 study published in The New England Journal of Medicine, all 12 patients who had completed 6 months of dostarlimab at the time of the original report achieved a clinical complete response. None had required chemoradiotherapy or surgery, and no cases of progression or recurrence were reported during the available follow-up.²

Longer-term findings subsequently reinforced the potential of neoadjuvant PD-1 blockade as a nonoperative treatment strategy for selected patients with dMMR tumors.³

Biomarker Status Could Reshape Treatment Selection

Approximately 5% to 10% of rectal cancers are characterized by dMMR or MSI-H biology. These tumors have impaired mechanisms for repairing DNA replication errors, resulting in greater accumulation of mutations. This biology can increase tumor recognition by the immune system and contributes to the sensitivity of dMMR/MSI-H cancers to immune checkpoint inhibition.¹

Traditional treatment for locally advanced rectal cancer commonly incorporates chemotherapy, radiation, and surgery. Although these approaches can provide disease control, treatment can produce lasting consequences involving bowel and urinary function, sexual health, fertility, and quality of life.^1-4

Avoiding those interventions without compromising cancer control would represent a substantial shift in the treatment pathway for this biomarker-defined population. The AZUR-1 strategy instead places molecular testing at the beginning of treatment decision-making, using dMMR/MSI-H status to identify patients who may derive sufficient benefit from PD-1 blockade alone.

Implications for Oncology Pharmacy Practice

For oncology pharmacists, a potential dostarlimab indication in locally advanced rectal cancer would expand the role of checkpoint inhibition into an earlier, potentially curative-intent setting.

Pharmacists would remain central to assessing treatment appropriateness, educating patients about immune-related adverse events, and supporting monitoring throughout therapy. PD-1 inhibitors can cause immune-mediated toxicities involving multiple organ systems, requiring prompt recognition and management.⁵

The regulatory review also reinforces the growing importance of biomarker-directed treatment selection in gastrointestinal oncology. Confirming dMMR/MSI-H status before treatment initiation could determine whether a patient follows a conventional multimodal pathway or becomes eligible for an organ-preserving immunotherapy strategy.

Dostarlimab has previously received both Fast Track and Breakthrough Therapy designations from the FDA for dMMR/MSI-H locally advanced rectal cancer. The current priority review brings the therapy closer to a potential indication that could alter the treatment sequence for a small but clinically important subset of patients with rectal cancer.¹

REFERENCES

1. GSK. Jemperli (dostarlimab) accepted for priority review by the US FDA for dMMR/MSI-H locally advanced rectal cancer. Published August 24, 2026. Accessed August 24, 2026. https://www.gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-accepted-for-priority-review-by-the-us-fda/

2. Cercek A, Lumish M, Sinopoli J, et al. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022;386(25):2363-2376. doi:10.1056/NEJMoa2201445

3. Cercek A, Foote MB, Rousseau B, et al. Nonoperative Management of Mismatch Repair-Deficient Tumors. N Engl J Med. 2025;392(23):2297-2308. doi:10.1056/NEJMoa2404512

4. Negro S, Bergamo F, Dell'Atti L, et al. Quality of Life in Rectal Cancer Treatments: An Updated Systematic Review of Randomized Controlled Trials (2013-2023). Cancers (Basel). 2025;17(14):2310. Published 2025 Jul 11. doi:10.3390/cancers17142310

5. Jemperli (dostarlimab-gxly) prescribing information. GSK.https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF