A newly approved use for an immunotherapy could help some patients with locally advanced rectal cancer avoid chemotherapy, radiation and surgery, treatments that can have lasting effects on quality of life.

The U.S. Food and Drug Administration granted accelerated approval for Jemperli (dostarlimab-gxly), manufactured by GSK, for adults with previously untreated stage II or stage III locally advanced rectal cancer whose tumors have specific genetic characteristics that make them more responsive to immunotherapy.

To qualify for the treatment, patients must have tumors that are mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), as confirmed by an FDA-authorized test, a news release for the agency said. Published estimates indicate that approximately 3% of locally advanced rectal cancers have these characteristics.

At stage II or stage III, the cancer has grown into nearby tissue or spread to nearby lymph nodes but has not reached distant organs.

The approval could offer eligible patients an alternative to standard treatment, which often involves chemotherapy and radiation before surgery. Those treatments can affect bowel, urinary and sexual function as well as fertility. Surgery also carries the risk of serious, sometimes life-threatening complications, including poor healing, leaks where the bowel is reconnected and the need for a permanent colostomy in some patients.

“The FDA is committed to closing the gap between scientific progress and patient access, and that commitment has to show up not just in policy, but in the pace of our work,” said Acting FDA Commissioner Kyle Diamantas, J.D. in the release. “American patients deserve timely access to innovative treatments, and the Trump Administration is making that a reality. 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.”

Jemperli works by blocking a protein called PD-1 on immune cells, interrupting a signal cancer cells use to evade the immune system.

The treatment targets tumors with defects in their DNA repair systems. Normally, cells have mechanisms to identify and correct errors made when DNA is copied. When those systems fail, errors accumulate and produce proteins the immune system can recognize. This makes dMMR and MSI-H tumors particularly vulnerable to immunotherapy.

“Standard treatment for rectal cancer has major life-changing effects. For certain types of rectal cancer, this approval represents a groundbreaking option that avoids surgery, radiation and chemotherapy. This represents a significant benefit for patients and their families,” said Angelo de Claro, M.D., director of the FDA’s Oncology Center of Excellence. “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.”

The FDA's decision was based on interim results from AZUR-1 (NCT05723562), a phase 2 clinical trial involving 154 patients with previously untreated dMMR or MSI-H locally advanced rectal cancer. Participants received Jemperli alone, with up to nine doses administered every three weeks over six months.

After a median follow-up of more than two years, nearly three-fourths of the patients had not required surgery, radiation or chemotherapy. Median follow-up means that at least half of the participants had been monitored for longer than two years.

Researchers will need to follow patients for a longer period to determine how durable the treatment responses are and how frequently the cancer returns.

Earlier research at Memorial Sloan Kettering Cancer Center also found promising results. In that study (NCT04165772), 50 patients with previously untreated dMMR or MSI-H locally advanced rectal cancer received Jemperli alone.

None of the patients had detectable signs of cancer after treatment, and 93% maintained that cancer-free status for at least 12 months. Among the 27 patients followed for at least three years, only one experienced a recurrence, which occurred in the same area.

Despite the results, Jemperli carries risks. The treatment can cause the immune system to attack healthy organs and tissues, potentially resulting in severe or fatal reactions.

The most common side effects, reported in at least 15% of patients treated for this type of rectal cancer, were fatigue, rash, diarrhea and itching.

The FDA granted Priority Review to the application and designated Jemperli a Breakthrough Therapy for treating dMMR or MSI-H locally advanced rectal cancer.

The decision also marks the 11th drug approval following review under the Commissioner's National Priority Voucher pilot program, which aims to accelerate the evaluation of treatments addressing national public health priorities.

Because the approval was granted under the FDA's accelerated approval pathway based on interim clinical trial results, GSK must continue monitoring patients and provide further evidence that the treatment produces lasting clinical benefits.