A Study of LOXO-435 in Patients With Cancer With a Change in a Gene Called FGFR3
- Conditions
- rinary Bladder NeoplasmsNeoplasm MetastasisUreteral Neoplasms
- Registration Number
- JPRN-jRCT2031230098
- Lead Sponsor
- Masaki Takeshi
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 140
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 naive.
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Phase 1a: To determine the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of LOXO-435: Number of patients with dose-limiting toxicities (DLTs) [ Time Frame: During the first 21-day cycle of LOXO-435 treatment ]<br>Number of patients with DLTs<br>Phase 1b: To evaluate the preliminary antitumor activity of LOXO-435: Overall response rate (ORR) [ Time Frame: Up to approximately 30 months or 2.5 years ]<br>ORR per investigator assessed RECIST v1.1
- Secondary Outcome Measures
Name Time Method