This is an open-label, multi-center, phase 1a/b study in participants with FGFR3-altered advanced solid tumors, including metastatic urothelial cancer (mUC). The study will be conducted in 2 phases: Dose escalation (1a) and dose expansion (1b). Phase 1a will assess safety, tolerability, and pharmacokinetics of LOXO-435 to determine the recommended phase 2 dose (RP2D). Phase 1b will include 4 dose expansion cohorts of patients with prespecified activating FGFR3 alterations to evaluate the efficacy and safety of LOXO-435 at the RP2D. Cohort B will enroll pts with mUC and includes three cohorts to evaluate LOXO-435 as monotherapy (B1, B2) and in combination with pembrolizumab (B3). Cohort C will enroll pts with non-UC advanced solid tumors and includes a cohort to evaluate LOXO-435 as monotherapy (C1).
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435. LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse.