A Study of LOXO-435 in Patients With Cancer With a Change in a Gene Called FGFR3

Open to people ages 18 years and up

• Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor or blood sample that is deemed as actionable.
  • Cohort A (Dose Escalation): Presence of an alteration in FGFR3 or its ligands deemed as a clinically or potentially clinically relevant alteration by the treating Investigator.
  • Cohorts B1, B2 and B3 (Dose Expansion): Histological diagnosis of urothelial cancer that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.
  • Cohort C (Dose Expansion): Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.
• Measurability of disease:
  • Phase 1a: measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
  • Phase 1b: Measurable disease required as defined by RECIST v1.1
• Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country-specific regulations.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patient has received all standard therapies for which the patient was deemed to be an appropriate candidate by the treating Investigator; OR the patient is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies.
  • Cohort B1: Patients must have been previously treated with a FGFR inhibitor.
  • Cohort B2, B3, C1: Patients must be FGFR inhibitor naïve.

• Patients with primary central nervous system (CNS) malignancy
• Known or suspected history of uncontrolled CNS metastases
• Current evidence of corneal keratopathy or retinal disorder
• Have a history and/or current evidence of extensive tissue calcification
• Any serious unresolved toxicities from prior therapy
• Significant cardiovascular disease
• Prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF)
• Active uncontrolled systemic infection or other clinically significant medical conditions
• Patients who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment