Phase 1 Study of Oral LOXO-435 Alone or with Pembrolizumab and Enfortumab Vedotin in Advanced or Metastatic Solid Tumors with FGFR3 Gene Alterations

What this Trial Is About

Researchers are studying the safety, side effects, and effectiveness of LOXO-435 alone or combined with standard cancer medicines in participants with advanced solid tumors that have changes in the FGFR3 gene. This includes cancers of the urinary system such as metastatic urothelial cancer. The study is an open-label phase 1 trial conducted in two parts dose escalation and dose expansion, focusing on finding the best dose and evaluating initial antitumor activity. Participants will receive LOXO-435 orally, either alone or with pembrolizumab and enfortumab vedotin administered intravenously, depending on their group. The study includes a dose escalation phase to determine the optimal dose and a dose expansion phase with several cohorts testing different combinations. Treatment continues for up to 30 months or longer if the disease does not worsen. During the study, participants will undergo assessments including safety monitoring, tumor response evaluation, pharmacokinetics testing, and quality of life questionnaires related to bladder symptoms and physical function. Researchers will track side effects and treatment impact over time, with visits scheduled regularly throughout treatment and follow-up. Participation may last up to 2.5 years, with ongoing monitoring of tumor response and safety.

FORAGER-1: A Study of LOXO-435 (LY3866288) in Participants With Cancer With a Change in a Gene Called FGFR3