A Study of LOXO-435 in Participants With Cancer With a Change in a Gene Called FGFR3
Study Phase: Phase 1
Recruitment Status: Recruiting
Start Date: January 19, 2023
End Date: June 01, 2025
Inclusion Criteria:
- Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor or blood sample that is deemed as actionable.
- Cohort A1 (Dose Escalation): Presence of an alteration in FGFR3 or its ligands.
- Cohort A2 (Dose Optimization): Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 alteration.
- 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:
- Cohort A1: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
- Cohorts A2, B1, B2, B3, and C1: 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.
- Prior Systemic Therapy Criteria:
- Cohort A1/C1: Participant has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating Investigator; OR the participant 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 A2/B1/B2/B3: Participants must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.
- FGFR inhibitor specific requirements:
- Cohort A1/A2: Prior FGFR inhibitor treatment is permitted, but not required.
- Cohort B1: Participants must have been previously treated with a FGFR inhibitor.
- Cohort B2, B3, C1: Participants must be FGFR inhibitor naïve.
Exclusion Criteria:
- Participants 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.
- Participants who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment. Participants who have stopped breastfeeding may be enrolled.