GSK’s Phase II AZUR-1 trial showed Jemperli achieved durable complete responses in dMMR/MSI-H rectal cancer, supporting regulatory submissions.
Written By: Shaik Jasmeen, PharmD
Reviewed By: Pharmacally Editorial Team
GSK has reported positive interim results from the registrational Phase II AZUR-1 trial (NCT05723562) evaluating Jemperli (dostarlimab) in patients with stage II/III mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer, marking another milestone for immunotherapy in early-stage colorectal cancer.
The global, single-arm study met its primary endpoint by demonstrating a clinically meaningful and durable clinical complete response at 12 months (cCR12). Patients achieving a clinical complete response remained free of detectable signs of cancer for at least one year after treatment, supporting the potential for dostarlimab to eliminate or delay the need for chemotherapy, radiation, and surgery in selected patients.
Based on these findings, GSK plans to submit the interim data to regulatory authorities worldwide, including the U.S. Food and Drug Administration (FDA), where the program is eligible for accelerated review.
Immunotherapy could reduce treatment burden
Rectal cancer affects an estimated 730,000 people worldwide each year, with approximately 5% to 10% of cases classified as dMMR/MSI-H. These tumors have defective DNA mismatch repair mechanisms, leading to high mutation rates that make them particularly responsive to immune checkpoint blockade.
Current treatment for locally advanced rectal cancer generally combines chemotherapy, radiation therapy, and surgery. Although effective, these interventions often result in permanent bowel dysfunction, colostomy, infertility, and other long-term quality-of-life consequences. The AZUR-1 findings suggest that immunotherapy alone may provide durable disease control while preserving organ function in appropriately selected patients.
AZUR-1 met its primary efficacy objective
AZUR-1 is a global, open-label, single-arm registrational Phase II trial enrolling patients with stage II/III dMMR/MSI-H locally advanced rectal cancer.
The study evaluated whether dostarlimab monotherapy could produce sustained clinical complete responses lasting at least 12 months without requiring standard chemoradiotherapy or surgery.
A total of 154 participants received nine cycles of dostarlimab over six months, administered as a 500 mg intravenous infusion every three weeks.
According to the interim analysis, the trial achieved its primary objective, with clinical outcomes substantially exceeding historical results reported with conventional multimodal treatment. The safety profile remained consistent with the established experience for dostarlimab across solid tumors, with no new safety signals identified.
Results build on earlier proof-of-concept studies
The AZUR-1 findings extend earlier clinical observations from Memorial Sloan Kettering Cancer Center, where dostarlimab first demonstrated complete clinical responses without additional therapy in patients with dMMR/MSI-H locally advanced rectal cancer.
Hesham Abdullah, Senior Vice President and Global Head of Oncology R&D at GSK, said the interim data reinforce the potential for dostarlimab to transform treatment for this molecularly defined patient population by allowing some patients to avoid therapies associated with substantial long-term morbidity while remaining free of detectable disease.
Regulatory pathway moves forward
Dostarlimab has already received FDA Breakthrough Therapy and Fast Track designations for dMMR/MSI-H locally advanced rectal cancer. GSK will present the full AZUR-1 dataset at a future scientific congress and submit the interim results to global health authorities to support regulatory review.
Jemperli is currently approved for multiple oncology indications but is not yet approved anywhere in the world for the treatment of rectal cancer. If regulators confirm the benefit observed in AZUR-1, the therapy could become the first immunotherapy capable of replacing standard chemoradiotherapy and surgery for a subset of patients with locally advanced dMMR/MSI-H rectal cancer.
What This Means for Patients
If confirmed by regulators, Jemperli (dostarlimab) could offer some patients with dMMR/MSI-H locally advanced rectal cancer a chance to avoid chemotherapy, radiation, and surgery while remaining free of detectable cancer. This approach may help preserve bowel function, fertility, and overall quality of life, although the treatment is not yet approved for rectal cancer and longer-term follow-up is still needed.
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About the Writer
Shaik Yasmeen (LinkedIn) is a Pharm.D graduate with interests in clinical pharmacy, pharmacovigilance, and medical writing. She has gained experience through hospital clinical postings, patient case reviews, case presentations, and literature evaluation. Passionate about evidence-based healthcare, she is committed to creating accurate and engaging medical content while continuously expanding her professional knowledge.