The FDA has approved dostarlimab-gxly, marketed as Jemperli, as the first immunotherapy treatment used alone for adults with untreated stage II or III rectal cancer that has not spread to distant organs but has grown into nearby tissue or lymph nodes. This approval applies specifically to patients whose tumors show mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) status, conditions found in about 3% of these cancers. These genetic features impair the cancer cells’ ability to repair DNA errors, making them more recognizable to the immune system. By targeting the PD-1 protein on immune cells, dostarlimab helps prevent tumors from hiding from the body’s defenses.
Support for the decision comes from interim findings of the AZUR-1 phase 2 trial, which involved 154 patients treated exclusively with dostarlimab. Patients received up to 9 doses, administered every 3 weeks over a 6-month period. After more than two years of observation, roughly three-quarters of participants had not needed surgery, radiation therapy, or chemotherapy. However, the FDA stressed that additional long-term data are necessary to determine how durable these responses remain and whether cancer might reappear later.
Previous studies at Memorial Sloan Kettering Cancer Center had already demonstrated promising results with dostarlimab in 50 patients with the same cancer type. None showed signs of cancer after treatment, and 93% stayed free of cancer for at least 12 months. Among 27 patients monitored for three years, only one experienced a recurrence, and it occurred at the original tumor site. The approach has since been incorporated into clinical guidelines, marking a shift in standard care for these patients.
Common side effects linked to dostarlimab include immune-related reactions such as fatigue, skin rashes, diarrhea, and itching, reported in at least 15% of patients. The drug’s approval was granted under an accelerated process, requiring the manufacturer, GSK, to continue tracking patients to confirm lasting benefits. The FDA completed its review nearly four months ahead of schedule due to the priority review and breakthrough therapy designations, reflecting the urgency and potential impact of the treatment.
This marks the 11th approval under the FDA’s National Priority Voucher program, which prioritizes therapies addressing critical public health needs. The agency noted that while dostarlimab offers a promising alternative to traditional treatments, further research remains essential to validate its long-term effectiveness and ensure patient outcomes are sustained over time.