FORAGER-1: A Study of LOXO-435 for Cancers with FGFR3 Gene Changes
This study, called FORAGER-1, is looking at a new medicine called LOXO-435. It's being tested alone or with other standard cancer medicines like pembrolizumab and enfortumab vedotin. The main goal is to see how safe LOXO-435 is, what side effects it might cause, and how well it works against certain cancers. This includes bladder cancer and other solid tumors that have a specific change in a gene called FGFR3. To join, you must have a solid tumor cancer with this FGFR3 gene change. The study will last up to 30 months (2.5 years), and possibly longer if your cancer doesn't get worse.
- Study design
- This is an open-label, multi-center study with a planned enrollment of 535 participants. It has two phases: Phase 1a to find the right dose of LOXO-435, and Phase 1b to test its effectiveness and safety.
- What's involved
- Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse. The study involves receiving LOXO-435 (oral), pembrolizumab (IV), or enfortumab vedotin (IV).
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will track side effects and how well the treatment works for up to approximately 30 months or 2.5 years.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT05614739
FORAGER-1: A Study of Vepugratinib (LY3866288; LOXO-435) in Participants With Cancer With a Change in a Gene Called FGFR3
Recruiting
PHASE1Ages 18+InterventionalTreatmentEli Lilly and Company
~677 participants
Updated 2026-08-20 on ClinicalTrials.gov
What's tested:VepugratinibPembrolizumabenfortumab vedotinTrastuzumab DeruxtecanMidazolamDigoxin
At a glance
Recruiting sites
82 of 82 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Overall Response Rate (ORR)
Measured over Up to Approximately 30 Months or 2.5 Years
+3 more outcomes measured
Conditions
Where it's being run
82 sites across 34 statesChina8
New York7
California5
Pennsylvania5
Spain5
Australia4
Japan4
South Korea4
Study leadership
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST) · STUDY_DIRECTOR · Eli Lilly and Company
Who to contact
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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.
Cohort B7: Urothelial cancer that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration and expression of human epidermal growth factor receptor 2 (HER2).
Cohort B8: Low Grade Intermediate Risk Non-Muscle Invasive Bladder cancer and a qualifying FGFR3 genetic alteration.
Measurability of disease:
Cohort A1, D1, and D2: 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, B7, and C1: Measurable disease required as defined by RECIST v1.1.
Cohort B8: Baseline disease which includes at least 1 lesion.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of:
0 or 1 for Cohorts A1, A2, B5, B6, B7, and B8.
Less than or equal to 2 for Cohorts B1, B2, B4, C1, DI and D2.
Cohort B6: Must be eligible for radical cystectomy plus pelvic lymph node dissection and agree to undergo curative intent standard radical cystectomy plus pelvic lymph node dissection.
Exclusion
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.
Cohort D1 only:
Have had renal transplantation.
Have a known history of nephrotic syndrome.
Have uncontrolled fluid overload, including clinically significant ascites, pleural effusion, or peripheral edema.
Have uncontrolled hypertension.
Are on hemodialysis or similar.
Cohort D2 only:
Have a history of:
Ventricular tachycardia or ventricular fibrillation.
Hypertrophic obstructive cardiomyopathy unless managed concurrently with atrial fibrillation.
Wolff-Parkinson-White syndrome.
Second- or third-degree atrioventricular block unless a functioning pacemaker is in place.
Heart rate less than (\<) 50 bpm.
Have any of these medical conditions:
Severe respiratory insufficiency.
Sleep apnea syndrome.
Myasthenia gravis.
Acute narrow-angle glaucoma.
Active liver disease or clinically significant hepatic impairment.
History of myopathy or rhabdomyolysis with any HMG-CoA reductase inhibitor.
What this trial measures
- Overall Response Rate (ORR)Up to Approximately 30 Months or 2.5 Years
- Pharmacokinetics (PK) of Vepugratinib: Area Under the Concentration versus Time Curve (AUC)Up to 2 Months
- PK of Midazolam, Rosuvastatin, and Digoxin Administered Alone and in the Presence of Vepugratinib: Area Under the Concentration versus Time Curve (AUC[0-inf])Up to 2 Months
- Complete Response Rate (CRR) in Participants with Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer (LG IR NMIBC)Up to approximately 24 months or 5 years