FDA Grants Accelerated Approval for GSK’s Jemperli in Biomarker-Defined Locally Advanced Rectal Cancer

The U.S. Food and Drug Administration on Oct. 19 granted accelerated approval to GSK’s Jemperli for a narrowly defined group of rectal cancer patients, a decision that could allow some of them to avoid chemotherapy, radiation and surgery. The new use is notable because standard treatment for locally advanced rectal cancer can leave patients with lasting quality-of-life effects.

The approval covers single-agent Jemperli, also known as dostarlimab-gxly, for adults with previously untreated stage II or stage III locally advanced rectal cancer whose tumors are mismatch repair deficient, or dMMR, or microsatellite instability-high, known as MSI-H. Patients must be identified using an FDA-authorized test. The decision does not apply broadly to all rectal cancer patients, but to this newly diagnosed, biomarker-defined subgroup.

The FDA said the approval was based primarily on interim results from AZUR-1, a global, open-label, single-arm phase 2 trial in 154 patients with previously untreated stage II or III dMMR/MSI-H locally advanced rectal cancer. Patients received up to nine doses of dostarlimab every three weeks over about six months. After a median follow-up of more than two years, the agency said almost three-fourths of patients in the study had not needed surgery, radiotherapy or chemotherapy.

The agency also pointed to earlier evidence from Memorial Sloan Kettering Cancer Center, where researchers reported strong responses in 50 patients. The FDA said none had detectable signs of cancer after treatment, 93% remained cancer-free for at least 12 months, and among 27 patients followed for at least three years, one had a recurrence.

Because the decision is an accelerated approval, it rests on interim evidence rather than full confirmation of long-term clinical benefit. Continued follow-up and confirmatory evidence will be required to verify how durable the responses are and whether the treatment’s benefit holds up over time.

The approval builds on years of research showing that dMMR/MSI-H tumors are especially responsive to PD-1 checkpoint inhibitors, a class of immunotherapy drugs that includes dostarlimab. It also follows high-profile Memorial Sloan Kettering research that drew wide attention in 2022 after an initial small group of rectal cancer patients had complete clinical responses after six months of treatment. Still, the newly approved use applies to a small slice of patients: The FDA said published estimates suggest about 3% of locally advanced rectal cancers are dMMR/MSI-H.

“Standard treatment for rectal cancer has major life-changing effects. For certain types of rectal cancer, this approval represents a groundbreaking option that avoids surgery, radiation and chemotherapy. This represents a significant benefit for patients and their families,” said Dr. Angelo de Claro, director of the FDA’s Oncology Center of Excellence.

The application received Priority Review and Breakthrough Therapy designation. But the drug also carries important safety warnings. The FDA said Jemperli can cause immune-mediated adverse reactions that can be severe or fatal, a risk seen with checkpoint inhibitors as the immune system is stimulated to attack cancer. In this rectal cancer population, the most common side effects were fatigue, rash, diarrhea and itching.