Bladder Cancer Clinical Trial
A Study of LOXO-435 in Patients With Cancer With a Change in a Gene Called FGFR3
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.
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).
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 naÃ¯ve.
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
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