FORAGER-1: A Study of Vepugratinib (LY3866288; LOXO-435) in Participants With Cancer With a Change in a Gene Called FGFR3
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorEli Lilly and Company
About this trial
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of Vepugratinib by itself or when it is combined with other medicines that treat cancer. Vepugratinib 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). Study participation could last up to approximately 6 years, depending on which part of the study you join.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Cohort A1, C1, D1, and D2: Locally advanced or metastatic solid tumor malignancy with a qualifying FGFR3 alteration.
Cohort A2, B2, B5 and B7: Urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration.
Cohorts B1 and B4: Urothelial cancer that is locally advanced or metastatic and have received prior erdafitinib.
Cohort B6: Muscle Invasive Bladder Cancer with a qualifying FGFR3 alteration.
Disqualifiers
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.
Trial design
Design model
Sequential
Treatments tested in this trial
Vepugratinib
DrugOral
Pembrolizumab
DrugIV
enfortumab vedotin
DrugIV
Trastuzumab Deruxtecan
DrugIV
Midazolam
DrugOral
Digoxin
DrugOral
Rosuvastatin
DrugOral
Treatment groups
677 Participants
are divided into 8 treatment groups8
Treatment groupsSee each treatment group below.
Group A: Phase 1a: Cohort A1 Vepugratinib Monotherapy Dose EscalationExperimental treatment 1 intervention
Group B: Phase 1a: Cohort A2 Vepugratinib Monotherapy Dose OptimizationExperimental treatment 1 intervention
Group C: Phase 1b: Cohort B1, B2, B4, C1, and D1 Vepugratinib Monotherapy Dose ExpansionExperimental treatment 1 intervention
Group D: Phase 1b: Cohort B5 Vepugratinib Plus Pembrolizumab Plus Enfortumab VedotinExperimental treatment 3 interventions
Group E: Phase 1b: MIBC Cohort B6 Vepugratinib Plus Pembrolizumab Plus Enfortumab VedotinExperimental treatment 3 interventions
Group F: Experimental: Phase 1b: Cohort B7 Vepugratinib Plus Trastuzumab DeruxtecanExperimental treatment 2 interventions
Group G: Phase 1b: NMIBC Cohort B8 Vepugratinib Monotherapy Dose ExpansionExperimental treatment 1 intervention
Group H: Phase 1b: Cohort D2 (Drug to Drug Interaction)Experimental treatment 4 interventions
Trial outcomes
Primary outcomes
1
Overall Response Rate (ORR)
Time frame
Up to Approximately 30 Months or 2.5 Years2
Pharmacokinetics (PK) of Vepugratinib: Area Under the Concentration versus Time Curve (AUC)
Time frame
Up to 2 Months3
PK of Midazolam, Rosuvastatin, and Digoxin Administered Alone and in the Presence of Vepugratinib: Area Under the Concentration versus Time Curve (AUC[0-inf])
Time frame
Up to 2 Months4
Complete Response Rate (CRR) in Participants with Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer (LG IR NMIBC)
Time frame
Up to approximately 24 months or 5 yearsSecondary outcomes
1
Change from Baseline in Bladder-Related Symptoms, Measured by Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) Subscale (BlCS)
Time frame
Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 3 Day 1 (28 Day Cycles)2
Change from Baseline in Physical Function, Measured by FACT- Physical Well-Being Scale (PWB) Subscale
Time frame
Up to Approximately 30 Months or 2.5 Years3
Event-Free Survival (EFS) in Participants with Muscle Invasive Bladder Cancer (MIBC)
Time frame
Up to approximately 30 months or 2.5 yearsSponsors and contacts
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Source ClinicalTrials.gov