The U.S. Food and Drug Administration granted accelerated approval to GSK plc's Jemperli for certain adults with rectal cancer after 71% of trial patients avoided additional treatment without disease progression at an interim review.
The decision, announced Monday, Oct. 19, covers Jemperli (dostarlimab-gxly) alone for previously untreated stage II or III locally advanced disease. Patients' tumors must have mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H), confirmed by an FDA-authorized test. The FDA says published estimates suggest about 3% of locally advanced rectal cancers have either characteristic.
Those markers indicate problems with the tumor's DNA repair process that can make it more recognizable to the immune system. For eligible patients, Jemperli offers a chance to avoid chemotherapy, radiation and surgery, though the trial results do not show that every patient can do so.
In AZUR-1, a phase 2 trial of 154 patients, 110 had received no cancer treatment beyond Jemperli and had no disease progression at the interim review. Median follow-up was 26.3 months. Another 26 had surgery, with or without additional systemic therapy or radiation; a separate group of 13 received additional systemic therapy or radiation. One patient had progression without further treatment, and four withdrew or were lost to follow-up.
The trial also measured how long complete responses lasted. Independent reviewers recorded a complete response sustained for 12 months in 54 of 116 evaluable patients. Another 38 had a complete response but had not yet reached 12 months of follow-up. These figures measure a different outcome in an evaluable subset of the 154 patients, using 116 rather than 154 as the denominator.
Chemotherapy and radiation can affect bowel and urinary function, sexual health and fertility, while surgery can leave some patients with a permanent colostomy. Jemperli has risks of its own: GSK reported serious adverse reactions in 20% of trial patients, and 3% permanently stopped treatment because of adverse reactions. The FDA warned that immune reactions affecting healthy organs and tissues can be severe or fatal.
In a statement issued by GSK, Colorectal Cancer Alliance CEO Michael Sapienza said testing for the biomarkers at diagnosis would help patients learn whether Jemperli is an option.
AZUR-1 had no comparison group, and the FDA requires continued follow-up to confirm lasting benefit. The interim findings do not establish how Jemperli compares with standard care for survival or long-term recurrence. Regulatory reviews of the new use are ongoing in Canada, Israel, Switzerland and the United Kingdom.
GSK has listed detailed AZUR-1 results for a session at the European Society for Medical Oncology (ESMO) Congress in Madrid on Sunday, Oct. 25. The session runs from 5:15 to 6:45 a.m. ET (09:15 to 10:45 UTC).
