FDA Approves Jemperli: Rectal Cancer Without Surgery for Some

The Food and Drug Administration on Monday approved an immunotherapy that lets a small but real group of rectal cancer patients skip the three treatments doctors have relied on for decades: chemotherapy, radiation and surgery.

The drug is Jemperli (dostarlimab-gxly), made by GlaxoSmithKline. The FDA granted it accelerated approval as a stand-alone treatment for adults with previously untreated stage II or stage III locally advanced rectal cancer whose tumors are mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H). The agency finished its review nearly four months ahead of its February 2027 target date.

The decision rests on interim results from AZUR-1, a phase 2 study of 154 patients. After a median follow-up of more than two years, almost three-fourths of them had not needed surgery, radiation or chemotherapy, according to the FDA announcement.

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

Who qualifies for Jemperli instead of surgery?

Only a narrow slice of patients. The approval covers locally advanced disease, meaning the cancer has grown into nearby tissue or reached nearby lymph nodes but has not spread to distant organs. The tumor must also test dMMR or MSI-H on an FDA-authorized test. Published estimates put that group at roughly 3% of locally advanced rectal cancers, the FDA said.

Those terms describe a defect in how cancer cells fix copying errors in their DNA. When the repair system fails, mistakes pile up and produce proteins the immune system can recognize. That makes these tumors unusually vulnerable to drugs like Jemperli, which blocks PD-1, a protein cancer cells use to hide from immune attack.

The American Cancer Society estimates about 49,990 Americans will be diagnosed with rectal cancer in 2026. Only stage II and III cases count, and only 3% of those, so by rough arithmetic the eligible group is a few hundred to roughly a thousand patients a year. The number is small. The change for each of those patients is not.

Why avoiding surgery matters so much for rectal cancer

Rectal cancer treatment is hard on the body in ways that outlast the disease. Chemotherapy and radiation before surgery can damage bowel, urinary and sexual function and affect fertility. Surgery carries the risk of poor healing and leaks where the bowel is reconnected, and for some patients it ends in a permanent colostomy.

Jemperli has its own risks. It can prompt the immune system to attack healthy organs, and those reactions can be severe or fatal. The most common side effects in the rectal cancer studies, reported in at least 15% of patients, were fatigue, rash, diarrhea and itching. Patients in AZUR-1 received up to nine infusions, one every three weeks over six months.

What the trials actually showed

The idea traces back to a small study at Memorial Sloan Kettering Cancer Center in New York. There, 50 patients with untreated dMMR or MSI-H locally advanced rectal cancer took Jemperli alone. None had detectable cancer afterward, and 93% stayed cancer-free for at least a year. Of 27 patients followed for three years or more, one had a recurrence, and it came back in the same area.

AZUR-1, the larger company-run trial registered as NCT05723562 on ClinicalTrials.gov, is designed to confirm those results in a bigger group. Because Monday’s approval is accelerated and based on interim data, GSK must keep following patients to show the responses translate into lasting benefit. The FDA said longer follow-up is still needed to understand how durable the responses are and how often the cancer returns.

The approval also marks the 11th drug cleared under the FDA’s National Priority Voucher pilot, a program meant to speed reviews of therapies the agency considers public health priorities. “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,” Acting FDA Commissioner Kyle Diamantas said.

What this means for patients and providers

• If you or a family member has a new rectal cancer diagnosis, ask whether the tumor has been tested for mismatch repair deficiency or microsatellite instability. The test is standard at most cancer centers, but the result decides whether this option is even on the table.
• The approval applies to stage II and III disease that has not been treated yet. It does not cover metastatic rectal cancer or tumors that are mismatch repair proficient, which is the large majority.
• Patients who respond still need close monitoring. The trials relied on frequent imaging and endoscopy to confirm the cancer had cleared and stayed cleared.
• For oncology practices and hospitals, the approval shifts a small group of surgical cases toward medical oncology and infusion services, with a six-month dosing schedule and ongoing surveillance built in.

Cancer centers have spent the past two years watching this data mature. For the broader picture on where cancer treatment is heading, see our earlier report on the latest cancer research breakthroughs, and our coverage of another fast-tracked FDA decision, the approval of the twice-yearly HIV prevention shot Yeztugo.

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