FGFR3 Inhibitor
LOXO-435
Phase
1
Enrolling
An Open-Label, Multicenter Study of LOXO-435 (LY3866288) in Advanced Solid Tumor Malignancies With FGFR3 Alterations*
Related Resources:
Key Inclusion Criteria
- 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 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): 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 version 1.1 (RECIST v1.1)
- Cohorts A2, B1, B2, B3, and C1: Measurable disease as defined by RECIST v1.1
- Adequate archival tumor tissue sample available or undergo a screening biopsy, if allowed per country-specific regulations
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Prior systemic therapy criteria:
- Cohorts A1 and C1: Participant has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating investigator; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies
- Cohorts A2, B1, B2, and 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:
- Cohorts A1 and A2: Prior FGFR inhibitor treatment is permitted, but not required
- Cohort B1: Participants must have been previously treated with a FGFR inhibitor
- Cohorts B2, B3, and C1: Participants must be FGFR inhibitor naïve
Key Exclusion Criteria
- Primary central nervous system (CNS) malignancy
- Uncontrolled CNS metastases
- Current evidence of corneal keratopathy or retinal disorder
- History and/or current evidence of extensive tissue calcification
- Any unresolved serious 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
- 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
*
This clinical trial is being conducted globally.
†
LOXO-435 is administered PO.
‡
Patients in cohort A2 will be randomized to dose levels chosen by the investigator.
§
Pembrolizumab is administered intravenously.
