The United States (US) Food and Drug Administration (FDA) granted accelerated approval on October 19, 2026, to dostarlimab (Jemperli, GSK) for adults with Stage II/III locally advanced rectal cancer (LARC) that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), as determined by an FDA-authorized test for solid tumors. The decision was supported by data from the pivotal AZUR-1 trial and a corroborating investigator-led study, and was approved four months ahead of the FDA goal date.
In the primary registration trial, 47% of evaluable patients achieved a sustained clinical complete response (cCR) at 12 months (cCR12) per independent central review (ICR). A key caveat is that 33% of additional patients who achieved cCR had less than 12 months of follow-up at the data cutoff, meaning the final proportion of durable responders may be higher than currently confirmed. Notably, 71% of all treated patients received dostarlimab alone, required no further treatment, and experienced no disease progression.
Key finding
In the AZUR-1 trial, dostarlimab monotherapy produced a cCR12 rate of 47% per ICR in MSI-H/dMMR Stage II/III LARC, with an additional 33% of patients achieving cCR but have not yet reached the 12-month follow-up threshold at data cutoff, and with no disease progression observed in any patient who achieved cCR12, cCR, or near-complete response over a median follow-up of 26.3 months.
Study Design
| Trial | AZUR-1 (NCT05723562); multicenter, single-arm, open-label |
|---|---|
| Population | 154 adults with previously untreated, histologically confirmed, MSI-H/dMMR Stage II/III locally advanced rectal cancer |
| Treatment | Dostarlimab 500 mg intravenously every 3 weeks for up to nine cycles |
| Primary endpoint | Sustained cCR12 per ICR, measured from the first post-treatment assessment at which cCR was observed |
| Key secondary endpoints | cCR12 per investigator assessment; objective response rate (ORR) per ICR and per investigator |
Tumor response was assessed using a multimodal approach combining endoscopy, rectal magnetic resonance imaging (MRI), and computed tomography (CT) imaging of the chest, abdomen, and pelvis at weeks 6, 12, and approximately 3 weeks after the final dose. Patients achieving cCR at either of the first two post-treatment assessments entered a nonoperative management period with surveillance conducted every four months for the first two years and every six months thereafter. Those who did not achieve cCR, or whose disease recurred or progressed, were evaluated for standard-of-care management by investigator discretion. The FDA also reviewed a supporting investigator-led trial (NCT04165772) that enrolled 50 patients with the same disease profile who received the same dostarlimab regimen.
Results and Safety
Among the 116 patients evaluable by ICR in AZUR-1, the cCR12 rate was 47% (95% CI: 27%-56%), with an additional 38 patients (33%) having achieved cCR with less than 12 months of follow-up at data cutoff. Another 44 patients (38%) achieved near-complete response. With a median follow-up of 26.3 months, no disease progression events were observed among patients who achieved cCR12, cCR, or near-complete response. The ORR per ICR was 79% (95% CI: 71%-85%). In the larger investigator-evaluable population of 144 patients, the cCR12 rate was 68% (95% CI: 60%-76%) and the ORR was 82% (95% CI: 75%-88%). Of 15 patients who proceeded to surgery following dostarlimab monotherapy due to imaging results suggestive of incomplete response, 12 achieved a pathological complete response.
The supporting investigator-led trial of 50 patients demonstrated a cCR12 rate of 93% (95% CI: 82%-99%) and an ORR of 100% (95% CI: 93%-100%), with no patients requiring chemoradiation or surgery. Among the 27 patients followed for at least three years, one experienced a local recurrence and was treated with lymphadenectomy, one withdrew, and one died from an unrelated cause.
The prescribing information for dostarlimab carries warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity. Detailed incidence data for specific adverse events were not disclosed in the FDA approval announcement.
Clinical Context
This approval marks a notable shift in the treatment paradigm for a molecularly defined subset of LARC. Historically, the standard approach for Stage II/III LARC has involved chemoradiation followed by surgery—a regimen associated with significant morbidity, including permanent colostomy in a proportion of patients. The AZUR-1 outcomes suggest that a meaningful fraction of patients with MSI-H/dMMR disease may achieve durable cCR with immunotherapy alone, potentially avoiding surgery and radiation altogether. The availability of an FDA-authorized companion diagnostic requirement for MSI-H/dMMR status underscores the biomarker-driven nature of patient selection.
However, several questions remain unanswered. The accelerated approval pathway means continued approval is contingent on verification of clinical benefit in confirmatory trials, and longer-term follow-up data will be needed to establish overall survival outcomes and the durability of organ-preserving responses beyond the current median follow-up of 26.3 months. The review was conducted under Project Orbis, with applications under ongoing review with Health Canada, Israel’s Ministry of Health, Switzerland’s Swissmedic, and the United Kingdom (UK)’s Medicines and Healthcare products Regulatory Agency, meaning the international regulatory picture has not yet been fully resolved.
Sources
- U.S. Food and Drug Administration. “FDA Grants Accelerated Approval to Dostarlimab for Locally Advanced Rectal Cancer.” Drug approval announcement. October 19, 2026. View source.
