FDA Approves Jemperli for dMMR Locally Advanced Rectal Cancer

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Jemperli (dostarlimab) for adults with stage 2 or 3 locally advanced rectal cancer that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), the agency announced on Oct. 19, 2026.

Patients must have their tumor's MSI-H or dMMR status confirmed with an FDA-authorized test for solid tumors before starting treatment.

The standard approach for locally advanced rectal cancer often combines chemotherapy, radiation and surgery, which can affect bowel, bladder and sexual function and sometimes requires a permanent ostomy. In the trial supporting this approval, most patients treated with Jemperli alone did not need any further treatment, meaning they could skip surgery and radiation entirely.

What is MSI-H/dMMR rectal cancer?

Tumors that are MSI-H or dMMR have trouble fixing errors in their DNA. That makes them more visible to the immune system, and immunotherapies like Jemperli, which release a brake on immune cells, tend to work especially well against them.

How the AZUR-1 trial tested jemperli in rectal cancer

The approval is based on AZUR-1, a multicenter, single-arm, open-label trial of 154 patients with previously untreated, MSI-H/dMMR stage 2 or 3 locally advanced rectal cancer. "Single-arm" means every patient received Jemperli; there was no comparison group.

Patients received 500 mg of Jemperli by IV every three weeks for nine cycles, unless their cancer progressed or side effects became too severe.

Doctors checked how tumors were responding with endoscopy, rectal MRI and CT scans of the chest, abdomen and pelvis. These checks happened at weeks 6 and 12, and again about three weeks after treatment ended.

Patients whose tumors disappeared on these tests, known as a clinical complete response, moved into a "watch-and-wait" period instead of having surgery. They were monitored with repeat exams every four months for the first two years and every six months after that. Patients without a complete response, or whose cancer returned or grew, could move on to standard treatment at their doctor's discretion.

What are the results of the study?

Of the 154 patients treated, 110 (71%) received Jemperli alone, needed no other treatment and did not see their cancer progress. Among the rest:

• 26 patients (17%) had surgery, with or without additional systemic therapy or radiation
• 13 patients (8%) received additional systemic therapy or radiation
• 1 patient had cancer progression without further treatment
• 4 patients (2.5%) withdrew or were lost to follow-up

The main goal of the study was a clinical complete response lasting at least 12 months, as judged by independent reviewers. Among 116 patients the reviewers could evaluate, 47% reached that milestone.

More patients may get there with time. Another 38 patients (33%) had a clinical complete response but had been followed for less than 12 months when the data were analyzed, and 44 patients (38%) had a near-complete response.

After a median follow-up of 26.3 months, none of the patients with a complete or near-complete response had seen their cancer progress.

Overall, 79% of patients had their tumors shrink, according to independent review. When the trial's own investigators assessed 144 patients, 68% had a 12-month sustained complete response and 82% had their tumors shrink.

Fifteen patients had surgery after Jemperli alone because imaging suggested their tumors had not fully responded. In 12 of them, no cancer was found in the tissue removed.

More data in dMMR rectal cancer

The FDA also reviewed a separate, investigator-led trial of 50 patients with the same type of rectal cancer who received the same Jemperli regimen. In that study, 93% had a complete response lasting at least 12 months, and every patient had their tumor shrink. No patients needed chemoradiation or surgery.

Of the 27 patients in that study followed for at least three years, one had a local recurrence treated with lymph node removal, one withdrew and one died of causes unrelated to rectal cancer.

Jemperli side effects and dosing

The recommended dose is 500 mg every three weeks for up to nine cycles, stopping earlier if the cancer progresses or side effects become too severe.

Jemperli's prescribing information includes warnings about immune-mediated side effects, which occur when the activated immune system attacks healthy organs. It also warns of infusion-related reactions, complications for patients who later receive a donor stem cell transplant, and potential harm to a developing fetus.

Patients should report new or worsening symptoms to their care team promptly, since immune-related side effects can often be managed when caught early.

What does an FDA accelerated approval mean for rectal cancer patients?

Accelerated approval lets the FDA approve treatments for serious conditions based on early signs of benefit, such as tumor response. Continued approval may depend on further studies confirming that benefit.

The FDA approved the application four months ahead of its goal date. Jemperli had received breakthrough therapy designation and priority review, and the application was part of the FDA Commissioner's National Priority Review Voucher pilot program.

The review was conducted under Project Orbis, which allows regulators in several countries to review cancer drugs at the same time. Health Canada, Israel's Ministry of Health, Switzerland's Swissmedic and the United Kingdom's Medicines and Healthcare products Regulatory Agency took part; their reviews are ongoing.

Jemperli is made by GlaxoSmithKline.

References

1. U.S. Food and Drug Administration. FDA grants accelerated approval to dostarlimab for locally advanced rectal cancer. Oct. 19, 2026.

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