Immunotherapy for dMMR Rectal Cancer
Chemotherapy, radiation and surgery cure many rectal cancers, but the price can include infertility, lifelong bowel trouble or a permanent colostomy. For a small group of patients whose tumors carry a specific DNA repair defect, the FDA has granted accelerated approval to GSK's Jemperli (dostarlimab-gxly) as a stand-alone first treatment that may let them skip all three.
.jpg){kind=link}
Key Takeaways
- The FDA approved Jemperli on October 19, 2026, for previously untreated adults with stage II or III rectal cancer that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H).
- In the phase 2 AZUR-1 trial of 154 patients, almost three-quarters needed no surgery, radiotherapy or chemotherapy after a median follow-up of more than two years.
- Because the approval rests on interim data, GSK must keep following patients to show the responses last; the FDA finished its review nearly four months early.
Who Qualifies
The approval covers adults whose cancer has grown into nearby tissue or reached nearby lymph nodes but has not spread to distant organs. An FDA-authorized test must confirm that the tumor is dMMR or MSI-H.
That group is small. Published estimates put it at about 3% of locally advanced rectal cancers, according to the FDA.
The defect is also the tumor's weak spot. Cells that cannot fix copying errors build up abnormal proteins, which the immune system can recognize. Jemperli blocks PD-1, a checkpoint protein on immune cells that tumors exploit to hide from attack.
What the Trials Showed
The decision rests on interim results from AZUR-1 (NCT05723562). Patients received up to nine infusions, one every three weeks over six months. After a median follow-up of more than two years, almost three-quarters had not needed surgery, radiotherapy or chemotherapy.
Fifteen patients went on to surgery because imaging suggested an incomplete response. In 12 of them, the removed tissue showed no remaining cancer.
Regulators also reviewed an earlier Memorial Sloan Kettering study of 50 patients. None had detectable cancer after treatment, and 93% stayed cancer-free for at least 12 months. Among 27 patients followed for three years or more, one saw the cancer return, in the same area.
Side Effects and Limits
Jemperli can turn the immune system against healthy organs, and those reactions can be severe or fatal. The most common side effects, reported in at least 15% of rectal cancer patients, were fatigue, rash, diarrhea and itching.
The FDA says longer follow-up is needed to show how long responses last and how often the cancer comes back.
A Review Four Months Early
GSK had expected a decision in February 2027. The application carried priority review and breakthrough therapy designation, and it became the 11th approval under the FDA Commissioner's National Priority Voucher pilot program.
“Completing this review nearly 4 months ahead of schedule means some patients who might otherwise be preparing for surgery, radiation or chemotherapy may now have a different conversation with their doctor,” said Acting FDA Commissioner Kyle Diamantas.
“The FDA is acting on emerging evidence to bring new approaches to patients sooner, while requiring further studies to confirm that these treatments provide lasting benefits,” said Angelo de Claro, director of the FDA's Oncology Center of Excellence.
“Today, Jemperli becomes the first and only approved immunotherapy for adults in the US with MSI-H/dMMR locally advanced rectal cancer,” said Tony Wood, GSK's chief scientific officer.
The approval arrives as rectal cancer shifts toward younger patients, for whom fertility and long-term bowel function weigh heavily. A 2026 American Cancer Society report found that rectal cancer now accounts for about a third of colorectal diagnoses, up from roughly a quarter in the mid-2000s, and that colorectal cancer incidence is rising 3% a year among adults aged 20 to 49.
The science moved quickly to get here. In 2022, a Memorial Sloan Kettering team reported that all 12 patients who completed dostarlimab treatment showed no evidence of tumor, a result that set up the larger trials behind this decision. Jemperli already held a 2021 accelerated approval for advanced dMMR solid tumors that had progressed after earlier therapy. Accelerated approvals can be withdrawn if confirmatory data fall short, so long-term recurrence figures from AZUR-1 now carry the weight.
Written by Alius Noreika