Gotistobart Combo Is Safe in Prostate Cancer, Phase 1 Data Show

A novel immunotherapy combination is proving to be both safe and manageable for patients with prostate cancer, according to updated phase 1 trial (NCT05682443) data presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. The study is evaluating gotistobart, a next-generation CTLA-4 targeting antibody, in combination with lutetium-based therapy.

David R. Wise, MD, PhD, the lead investigator from NYU Langone in New York, New York, discussed the findings, emphasizing that the primary goal of the initial phase was to assess safety. A key concern heading into the trial was the potential for compounded gastrointestinal toxicity, given that lutetium 177 can cause gastrointestinal issues and immunotherapies can trigger autoimmune-related adverse events (AEs) such as colitis.

“We really didn’t see any major surprises,” Wise explained. Although some patients did experience colitis and diarrhea, the AEs were manageable, he said. Crucially, the trial reported no grade 4 AEs and no deaths related to the study drug, a significant finding when combining treatments that can overstimulate the immune system.

Wise attributed this favorable safety profile to the unique mechanism of gotistobart. Unlike first-generation CTLA-4 inhibitors such as ipilimumab (Yervoy), which can cause widespread immune activation, gotistobart is designed to be a Treg depleter that works selectively within the tumor microenvironment.

“We think that’s important because the Tregs in the tumor are suppressing the anticancer response, whereas the Tregs circulating in the rest of the body are actually preventing excessive autoimmunity,” Wise said. The hope was that this targeted approach would yield a lower rate of high-grade toxicity, and based on the data so far, that hypothesis is holding true.

The randomized phase 1 study has now completed enrollment and is advancing as a phase 2 trial, with investigators encouraged by both the safety and early efficacy signals.