GSK (NYSE: GSK) reported positive interim results from the registrational AZUR-1 trial of dostarlimab (Jemperli) in patients with stage II/III mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) locally advanced rectal cancer — data that, if supported by regulators, ccould become the first approved immunotherapy to enable a non-operative treatment approach in a biomarker-selected rectal cancer population.
The Phase II single-arm trial enrolled 154 patients who received nine cycles of dostarlimab 500 mg intravenously every three weeks over six months. The trial met its primary objective: a meaningful and sustained clinical complete response rate at 12 months (cCR12), defined as no detectable signs of cancer one year or more after treatment. GSK described the result as "clinically significant" and consistent with historical comparisons, though specific numerical response rates were not disclosed. Full data will be presented at a future scientific congress. Safety was consistent with dostarlimab's established profile across solid tumor indications.
Dostarlimab (Jemperli) is a programmed death receptor-1 (PD-1) immune checkpoint inhibitor designed to restore T-cell-mediated anti-tumor immunity. The drug is already an established oncology asset for GSK, with approvals in the US for recurrent or advanced dMMR endometrial cancer after platinum-based chemotherapy, primary advanced or recurrent endometrial cancer in combination with carboplatin and paclitaxel followed by maintenance monotherapy, regardless of mismatch repair status, and for adults with recurrent or advanced dMMR solid tumors lacking satisfactory treatment alternatives. dMMR/MSI-H tumors accumulate large numbers of mutations, generating neoantigens that make them particularly susceptible to immune checkpoint blockade.
The significance of the AZUR-1 data lies in what these patients would otherwise face. Standard treatment for locally advanced rectal cancer consists of chemoradiotherapy followed by total mesorectal excision, an approach associated with permanent colostomy in some patients as well as bowel, urinary, sexual and fertility complications. The dMMR/MSI-H subtype accounts for approximately 5–10% of rectal cancers, or roughly 36,000–73,000 cases annually based on a global incidence of approximately 730,000 per year.
AZUR-1 builds on earlier work from Memorial Sloan Kettering Cancer Center, where a small investigator-initiated study first demonstrated that dostarlimab monotherapy could produce clinical complete responses without chemotherapy, radiation, or surgery in this population. That earlier signal attracted widespread attention when published in the New England Journal of Medicine in 2022, but lacked the scale and design to support regulatory approval. AZUR-1 was designed to provide that evidence.