The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Jemperli (dostarlimab-gxly) as a standalone treatment for certain adults with previously untreated stage II or stage III locally advanced rectal cancer, potentially allowing them to avoid surgery, radiation and chemotherapy.
The approval applies to patients whose tumors are mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), genetic characteristics that make cancer cells particularly susceptible to immunotherapy. These biomarkers must be confirmed using an FDA-authorized test.
Approximately 3% of locally advanced rectal cancers are estimated to have these characteristics, making the treatment an option for a relatively small but important group of patients.
Standard treatment for locally advanced rectal cancer often involves chemotherapy and radiation before surgery. Although these approaches can control the disease, they may also have lasting effects on bowel, urinary and sexual function, as well as fertility. Surgery can carry additional risks, including complications involving bowel healing and, in some cases, the need for a permanent colostomy.
Jemperli works by blocking the PD-1 protein on immune cells, helping the body's immune system recognize and attack cancer cells. Tumors with dMMR or MSI-H characteristics tend to accumulate DNA errors, producing abnormal proteins that can make them more recognizable to the immune system. The FDA said the approval could provide eligible patients with an alternative to treatments that may significantly affect their quality of life.
The FDA based its decision on interim findings from AZUR-1, a phase 2 clinical trial involving 154 patients with previously untreated dMMR or MSI-H locally advanced rectal cancer.
Participants received up to nine doses of Jemperli over six months, with treatments administered every three weeks. After a median follow-up exceeding two years, nearly three-quarters of patients had avoided surgery, radiation therapy and chemotherapy.
The findings suggest that immunotherapy alone may offer a treatment pathway that preserves organs and reduces the need for conventional interventions in selected patients. However, longer follow-up is necessary to determine how durable these responses are and how frequently cancer returns.
Earlier research conducted at Memorial Sloan Kettering Cancer Center also reported encouraging results. In that study, all 50 patients treated with Jemperli had no detectable signs of cancer after treatment. Nearly 93% maintained their cancer-free status for at least 12 months. Among the 27 patients followed for at least three years, one experienced a recurrence in the same area.
While these results are promising, the studies do not establish that every eligible patient can safely avoid conventional treatment indefinitely. Continued monitoring remains essential.
Despite its potential benefits, Jemperli carries significant safety risks. By activating the immune system against cancer, the drug can also cause immune cells to attack healthy organs and tissues. These reactions can be severe and, in some cases, fatal.
The most commonly reported side effects in patients treated for this type of rectal cancer included fatigue, rash, diarrhea and itching. Patients receiving the drug require careful medical supervision to identify and manage immune-related complications.
The FDA granted the application Priority Review and awarded Jemperli Breakthrough Therapy designation for dMMR or MSI-H locally advanced rectal cancer. The decision also marks the 11th drug approval under the agency's Commissioner's National Priority Voucher pilot program.
The accelerated approval was granted to GSK based on interim clinical trial findings. The company must continue following patients and provide additional evidence to establish whether the treatment delivers lasting clinical benefits.
For eligible patients, the approval represents a significant development in rectal cancer care, potentially offering a way to control the disease while avoiding treatments that can have substantial long-term consequences. Further research will determine how broadly this approach can be used and whether its benefits remain durable over time.
