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

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.

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.