FDA Grants Accelerated Approval to Dostarlimab for dMMR Rectal Cancer

The FDA has granted accelerated approval to dostarlimab-gxly (Jemperli; GSK) as monotherapy for adults with previously untreated stage II or III locally advanced rectal cancer that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), according to an agency announcement.¹ The approval may allow some patients to avoid chemotherapy, radiation, and surgery.

At stage II or III, the cancer has grown into nearby tissue or reached nearby lymph nodes but has not spread to distant organs. Eligible patients must have tumors that are dMMR or MSI-H, as determined by an FDA-authorized test. Published estimates suggest approximately 3% of locally advanced rectal cancers carry these features.

Both terms describe a defect in how cancer cells correct DNA copying errors. When that repair system fails, errors accumulate and produce proteins the immune system can recognize, which makes these tumors particularly vulnerable to immunotherapy. Dostarlimab targets the PD-1 protein on immune cells, blocking a signal that cancer cells use to evade immune attack.

AZUR-1 Results Supporting the Approval

The decision rests on interim results from AZUR-1 (NCT05723562), a phase 2 study of dostarlimab alone in 154 patients with previously untreated dMMR or MSI-H locally advanced rectal cancer. Patients received up to 9 doses, given every 3 weeks over 6 months.

After a median follow-up of more than 2 years, almost three-fourths of patients had not needed surgery, radiotherapy, or chemotherapy. The FDA noted that longer follow-up is needed to establish the duration of response and how often the cancer returns.

An earlier study at Memorial Sloan Kettering Cancer Center (NCT04165772) evaluated dostarlimab alone in 50 patients with the same disease profile. No patient had detectable cancer after treatment, and 93% maintained that cancer-free status for at least 12 months. Among the 27 patients followed for at least 3 years, only 1 had a recurrence, and it occurred in the same area.

Neoadjuvant PD-1 blockade was subsequently incorporated into National Comprehensive Cancer Network guidelines for dMMR locally advanced rectal cancer, and Andrea Cercek, MD, of Memorial Sloan Kettering has said the approach changed the treatment paradigm for these patients.²

Safety Profile of Dostarlimab

Dostarlimab can cause the immune system to attack healthy organs and tissues, and these reactions can be severe or fatal.¹ The most common adverse events, reported in at least 15% of patients treated for this type of rectal cancer, were fatigue, rash, diarrhea, and itching.

Standard care for locally advanced rectal cancer often includes chemotherapy and radiation before surgery. These treatments can affect bowel, urinary, and sexual function, as well as fertility. Surgery carries risks of serious and sometimes life-threatening complications, including poor healing, leaks where the bowel is reconnected, and in some patients, permanent colostomy.

“For certain types of rectal cancer, this approval represents a groundbreaking option that avoids surgery, radiation and chemotherapy,” Angelo de Claro, MD, director of the FDA’s Oncology Center of Excellence, said in a statement. He added that the agency is acting on emerging evidence while requiring further studies to confirm lasting benefit.

Regulatory Pathway and Confirmatory Requirements

The application received Priority Review, and dostarlimab holds Breakthrough Therapy designation for dMMR or MSI-H locally advanced rectal cancer. The FDA completed its review nearly 4 months ahead of schedule, according to Acting FDA Commissioner Kyle Diamantas, JD.

The approval is the 11th for a drug reviewed under the Commissioner’s National Priority Voucher pilot program, which is intended to accelerate review of therapies that address national public health priorities. Because the approval is accelerated and based on interim results, GSK must continue following patients to demonstrate that responses translate into lasting clinical benefit.

References

1. FDA grants accelerated approval to dostarlimab-gxly for locally advanced dMMR or MSI-H rectal cancer. News release. US Food and Drug Administration. October 19, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-immunotherapy-may-allow-certain-patients-rectal-cancer-avoid-chemotherapy-radiation-and

2. Joszt L. Immunotherapy advancements making strides in GI malignancies. Evid Based Oncol. Published December 19, 2023. Accessed October 19, 2026. https://www.ajmc.com/view/immunotherapy-advancements-making-strides-in-gi-malignancies