A Study of Vepugratinib (LY3866288) in Participants With Cancer in the Urinary Tract (FORAGER-2)

Lilly

Status and phase: Begins enrollment this month; Phase 3

Conditions: Urinary Bladder Neoplasms; Neoplasm Metastasis; Carcinoma, Transitional Cell

Treatments: Drug: Vepugratinib; Drug: EV; Drug: Pembrolizumab; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07218380

J4G-MC-JZVD (Other Identifier)

27333

2025-522855-25-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

The purpose of this study is to test a new medicine, vepugratinib, in comparison with placebo, to see if it is safe and can help people with a bladder cancer that is advanced or has spread.

Vepugratinib and placebo will be administered in combination with existing standard of care (SOC) therapy.

Study participation could last up to approximately 6 years.

Enrollment: 450 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have histologically confirmed, unresectable locally advanced or metastatic urothelial cancer (mUC). Individuals with mixed histology other than small cell or neuroendocrine carcinoma are eligible if a urothelial component is present.
• Have a qualifying fibroblast growth factor receptor 3 (FGFR3) genetic alteration determined via molecular testing from a tumor or blood sample obtained at or any time after diagnosis of advanced or metastatic urothelial cancer.
• Have measurable disease by investigator assessment defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Have adequate laboratory parameters

Exclusion criteria

• Have received prior systemic therapy for locally advanced or metastatic urothelial cancer (mUC).
• Have any unresolved toxicities greater than Grade 1 Common Terminology Criteria for Adverse Events ([CTCAE] version 5.0) from prior neoadjuvant or adjuvant systemic therapy.
• Have ongoing sensory or motor neuropathy of Grade 2 or higher
• Have untreated or uncontrolled central nervous system (CNS) involvement or any history of leptomeningeal disease.
• Current evidence corneal keratopathy or retinal disorder confirmed by ocular examination at screening.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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450 participants in 3 patient groups, including a placebo group

Vepugratinib + EV + Pembrolizumab (Safety Lead In)

Experimental group

Description:

Vepugratinib administered orally with EV + pembrolizumab administered IV

Treatment:

Drug: Pembrolizumab

Drug: EV

Drug: Vepugratinib

Vepugratinib + Enfortumab Vedotin (EV) + Pembrolizumab

Experimental group

Description:

Vepugratinib administered orally, and EV + pembrolizumab administered by intravenous (IV) infusion.

Treatment:

Drug: Pembrolizumab

Drug: EV

Drug: Vepugratinib

Placebo + EV + Pembrolizumab

Placebo Comparator group

Description:

Placebo administered orally, and EV + pembrolizumab administered by IV infusion.

Treatment:

Drug: Pembrolizumab

Other: Placebo

Drug: EV