FORAGER-1: A Study of Vepugratinib (LY3866288; LOXO-435) in Participants With Cancer With a Change in a Gene Called FGFR3
Study Phase: Phase 1
Recruitment Status: Recruiting
Start Date: January 12, 2023
End Date: June 01, 2027
Physicians interested in becoming principal investigators please contact
Inclusion Criteria:
- 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 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.
- 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.