NIPH Clinical Trials Search

FORAGER-1: A Study of LOXO-435 (LY3866288) in Participants With Cancer With a Change in a Gene Called FGFR3

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Urinary Bladder Neoplasms Neoplasm Metastasis Ureteral Neoplasms
Date of first enrollment	05/07/2023
Target sample size	535
Countries of recruitment	United States,Japan,Australia,Japan
Study type	Interventional
Intervention(s)	Drug: LOXO-435 Oral Other Name: LY3866288 Drug: Pembrolizumab IV Drug: enfortumab vedotin IV Experimental: Phase 1a: LOXO-435 Monotherapy Dose Escalation LOXO-435 administered orally Intervention: Drug: LOXO-435 Experimental: Phase 1a: Cohort A2 LOXO-435 Monotherapy Dose Optimization LOXO-435 administered orally Intervention: Drug: LOXO-435 Experimental: Phase 1b: Cohort B1,B2,B4 and C1 LOXO-435 Monotherapy Dose Expansion LOXO-435 administered orally Intervention: Drug: LOXO-435 Experimental: Phase 1b: Cohort B3 LOXO-435 Plus Pembrolizumab LOXO-435 administered orally in combination with pembrolizumab administered intravenously (IV) Interventions: Drug: LOXO-435 Drug: Pembrolizumab Experimental: Phase 1b: Cohort B5 LOXO-435 Plus Pembrolizumab Plus Enfortumab Vedotin LOXO-435 administered orally in combination with pembrolizumab administered IV and enfortumab vedotin administered IV Interventions: Drug: LOXO-435 Drug: Pembrolizumab Drug: enfortumab vedotin

Outcome(s)

Primary Outcome

Phase 1a: To determine the recommended dose of LOXO-435: Safety, number of participants with dose-limiting toxicities (DLTs) Number of participants with DLTs [Time Frame: Minimum of the first 21-day cycle of LOXO-435 treatment] Phase 1b: To evaluate the preliminary antitumor activity of LOXO-435: Overall response rate (ORR) ORR per investigator assessed RECIST v1.1 [Time Frame: Up to approximately 30 months or 2.5 years] Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration A summary of TEAEs and SAEs regardless of causality, will be reported in the Reported Adverse Events module [Time Frame: Up to approximately 30 months or 2.5 years]

Secondary Outcome

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	Not applicable
Gender	Both
Include 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: Presence of an alteration in FGFR3 or its ligands Cohort A2, B2, B3, and B5: Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration Cohorts B1 and B4: Histological diagnosis of urothelial cancer that is locally advanced or metastatic Cohort C1: Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration Measurability of disease: Cohort A1 and B3: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1) Cohorts A2, B1, B2, B4, B5, and C1: Measurable disease required as defined by RECIST v1.1 Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for Cohorts A1, A2, B3, and B5 Less than or equal to 2 for Cohorts B1, B2, B4, and C1 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, B2, B3 participants must have received at least one prior regimen, and cohorts B1 and B4 participants at least 2 prior regimens, in the locally advanced or metastatic setting There is no restriction on number of prior therapies Cohort B5: Participants have not received prior systemic therapy for locally advanced or metastatic UC FGFR inhibitor specific requirements: Cohort A1/A2/B3: Prior FGFR inhibitor treatment is permitted but not required Cohort B1/B4: Participants must have been previously treated with erdafitinib Cohort B2, B5, and C1: Participants must be FGFR inhibitor naive
Exclude criteria	Participants with primary central nervous system (CNS) malignancy Untreated or uncontrolled CNS metastases Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible 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