In what GSK says represents a potential way to transform treatment for patients with certain types of rectal cancer, the company’s Jemperli has met the main goal of a phase 2 trial, teeing up an application with the FDA.
Interim results from the phase 2 AZUR-1 study showed a “meaningful and sustained” clinical complete response rate for Jemperli at 12 months in stage 2/3 mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) locally advanced rectal cancer, GSK said Monday.
Without going into specifics, GSK said its PD-1 inhibitor showed a “substantial improvement” compared to historical experience with existing treatment options. The company now plans to share the data with global health authorities, including with the FDA under an accelerated approval pathway.
Current standard of care for locally advanced rectal cancer includes chemotherapy, radiation and surgery, which “can profoundly impact a patient’s quality of life, potentially leading to lifelong use of a colostomy bag, significant physiological dysfunction, and infertility,” the company said.
The latest data support the potential for Jemperli to “transform treatment for dMMR/MSI-H locally advanced rectal cancer,” demonstrating that “some patients may be able to avoid those interventions while remaining free of detectable signs of cancer,” GSK’s global head of oncology R&D, Hesham Abdullah, M.D., said in a July 13 statement.
DMMR/MSI-H locally advanced rectal cancer is not a large indication. The American Cancer Society estimates about 50,000 new cases of rectal cancer in the U.S. for 2026. About 5% to 10% of all rectal cancers show genetic mutations known as dMMR/MSI-H, according to GSK.
Jemperli’s potential in the small indication drew public attention from the likes of The New York Times in 2022 when researchers at Memorial Sloan Kettering Cancer Center reported complete remissions in all rectal cancer patients in a small trial.
The complete response rate stood at 100% among 42 patients in an update of the single-center study in 2024. At that time, the median follow-up time exceeded two years for the first 24 patients evaluated.
Based on the impressive—but early—initial data, GSK asked the FDA’s permission to allow it to file for accelerated approval using complete response data from a single-arm trial. In an unusual FDA oncologic advisory committee meeting, external experts voted 8 to 5 in support of that regulatory path in dMMR/MSI-H locally advanced rectal cancer.
During the 2023 meeting, the FDA’s advisers said they would prefer longer-term follow-up data than 12 months. Complete response rates at two years and three years, plus three-year event-free survival, are key secondary endpoints of the AZUR-1 study.
Alongside the phase 2 trial, GSK is conducting AZUR-2, a randomized phase 3 trial in dMMR/MSI-H resectable colon cancer. GSK has argued that colon cancer and rectal cancer are alike.
Colorectal cancers are predominantly cold tumors, meaning they lack immune cell infiltration and are therefore resistant to PD-1 inhibitors. But the defective DNA repair creates mutations and abnormalities that make colorectal tumors with dMMR immunogenic and susceptible to immunotherapies.
Both Jemperli and Merck & Co.’s Keytruda hold tumor-agnostic indications from the FDA covering dMMR metastatic solid tumors, including colorectal cancer.