GSK to Seek FDA Approval for Jemperli in Rectal Cancer After Phase 2 Success

GSK (GSK) said it plans to seek U.S. regulatory approval for its cancer immunotherapy Jemperli in a select group of rectal cancer patients, after the drug met the primary goal of a phase 2 clinical trial in what the company described as a potentially transformative advance for the indication.

Interim results from the AZUR-1 study showed a "meaningful and sustained" clinical complete response rate at 12 months in patients with stage 2 and 3 mismatch repair deficient, microsatellite instability-high — known as dMMR/MSI-H — locally advanced rectal cancer. GSK said the PD-1 inhibitor demonstrated a substantial improvement over historical outcomes with existing treatments, though the company did not disclose specific response figures ahead of a formal data presentation.

GSK said it now plans to share the results with global health authorities, including the U.S. Food and Drug Administration under an accelerated approval pathway.

The indication is a narrow one. The American Cancer Society estimates around 50,000 new cases of rectal cancer in the U.S. in 2026, with dMMR/MSI-H tumors accounting for roughly 5% to 10% of that total. Nevertheless, the patient population has attracted significant scientific and public interest since 2022, when researchers at Memorial Sloan Kettering Cancer Center reported complete remissions in every patient enrolled in a small single-center trial. An update published in 2024 showed the complete response rate held at 100% across 42 patients, with a median follow-up exceeding two years for the first cohort evaluated.

Current standard of care for locally advanced rectal cancer typically involves a combination of chemotherapy, radiation and surgery — a regimen that GSK said can lead to lifelong colostomy bag use, significant physiological dysfunction and infertility. Hesham Abdullah, GSK's global head of oncology research and development, said the AZUR-1 data demonstrated that "some patients may be able to avoid those interventions while remaining free of detectable signs of cancer."

The path to accelerated approval has not been straightforward. GSK previously sought the FDA's permission to file on the basis of complete response data from a single-arm trial — an unusual regulatory strategy that required sign-off from an FDA oncologic advisory committee. External experts voted 8 to 5 in favor of that approach in 2023, though advisers at the time indicated a preference for follow-up data beyond 12 months. Complete response rates at two and three years, along with three-year event-free survival, remain key secondary endpoints in AZUR-1.

In parallel, GSK is running AZUR-2, a randomized phase 3 trial examining Jemperli in dMMR/MSI-H resectable colon cancer, a related but distinct setting. The company has argued that the biology of colon and rectal cancers is sufficiently similar to support a broader development program.

The dMMR/MSI-H subtype is particularly amenable to immunotherapy because defective DNA repair mechanisms generate high levels of tumor mutations, making these cancers recognizable to the immune system despite colorectal tumors being broadly considered "cold" — typically lacking the immune cell infiltration that PD-1 inhibitors require to be effective.

Jemperli already holds a tumor-agnostic FDA approval covering dMMR metastatic solid tumors, an indication it shares with Merck & Co.'s (MRK) Keytruda, the world's best-selling cancer drug.