Some Rectal Cancer Patients May Skip Surgery After FDA Approval

Keypoints:

• The Food and Drug Administration (FDA) granted accelerated approval to Jemperli (dostarlimab) on 19 October
• It covers stage II or III locally advanced rectal cancer with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H)
• In the 154-patient AZUR-1 trial, 71% needed no other treatment and had no progression
• The biomarker appears in about 5% to 10% of rectal cancers
• The FDA approved it about four months ahead of its February 2027 target date

The FDA granted accelerated approval to GSK's immunotherapy Jemperli on Monday. It is approved as a single treatment for adults with previously untreated stage II or III locally advanced rectal cancer. The tumor must be mismatch repair deficient or microsatellite instability-high, as shown by an FDA-authorized test. Jemperli is now the first immunotherapy approved for this group.

Standard treatment is demanding. Patients usually get chemotherapy and radiation before surgery. Those treatments can leave lasting effects, including bowel, urinary and sexual dysfunction, secondary cancers and infertility. The FDA noted that completing its review nearly four months early means some patients may now have a different conversation with their doctor.

The approval rests on AZUR-1, a phase 2 trial in 154 patients. Participants received up to nine doses of Jemperli, one every three weeks over six months. With a median follow-up of more than two years, 110 patients (71%) received Jemperli alone, needed no other treatment and had no disease progression. Another 26 (17%) had surgery, and 13 (8%) received more systemic therapy or radiation. The FDA also reviewed a smaller investigator-led trial of 50 patients.

The mechanism is specific. Dostarlimab blocks the PD-1 protein on immune cells, which removes a shield that cancer cells use to hide. Tumors with mismatch repair deficiency carry a flaw in how they fix DNA errors. That flaw makes them more visible to the immune system once the shield drops. Jemperli was permanently discontinued because of side effects in 3% of patients.

The caveats are important. This is an accelerated approval based on a single-arm study with no comparison group. Further data is needed to confirm the benefit. Full interim results are due at the European Society for Medical Oncology Congress this month. Only the 5% to 10% of rectal cancer patients with this biomarker qualify.