FORAGER-1: A Study of LOXO-435 (LY3866288) 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 LOXO-435 by itself or when it is combined with other standard medicines that treat cancer. 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
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
LOXO-435
DrugOral
Pembrolizumab
DrugIV
enfortumab vedotin
DrugIV
Treatment groups
535 Participants
are divided into 5 treatment groupsGroup A: Phase 1a: Cohort A1 LOXO-435 Monotherapy Dose EscalationExperimental treatment 1 intervention
Group B: Phase 1a: Cohort A2 LOXO-435 Monotherapy Dose OptimizationExperimental treatment 1 intervention
Group C: Phase 1b: Cohort B1, B2, B4, and C1 LOXO-435 Monotherapy Dose ExpansionExperimental treatment 1 intervention
Group D: Phase 1b: Cohort B3 LOXO-435 Plus PembrolizumabExperimental treatment 2 interventions
Group E: Phase 1b: Cohort B5 LOXO-435 Plus Pembrolizumab Plus Enfortumab VedotinExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
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 treatment2
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 years3
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 yearsSecondary outcomes
1
To assess the pharmacokinetics (PK) of LOXO-435: Area under the concentration versus time curve (AUC)
PK of LOXO-435: AUC
Time frame
Up to 2 months2
To assess the PK of LOXO-435: Minimum plasma concentration (Cmin)
PK of LOXO-435: Cmin
Time frame
Up to 2 months3
To evaluate the preliminary antitumor activity of LOXO-435: Objective response rate (ORR)
ORR per investigator assessed RECIST 1.1
Time frame
Up to approximately 30 months or 2.5 years]4
To evaluate the preliminary antitumor activity of LOXO-435: Duration of response (DoR)
DOR per investigator assessed RECIST 1.1
Time frame
Up to approximately 30 months or 2.5 yearsSponsors and contacts
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Source ClinicalTrials.gov