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Vepugratinib with enfortumab vedotin and pembrolizumab for FGFR3‑altered advanced urothelial cancer

FORAGER-2: A Phase 3, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Vepugratinib Combined With Enfortumab Vedotin and Pembrolizumab in Adults With Untreated Locally Advanced or Metastatic Urothelial Carcinoma With an FGFR3 Genetic Alteration

Phase 3 Interventional Eli Lilly and Company · NCT07218380

This trial tests whether adding vepugratinib to enfortumab vedotin and pembrolizumab helps people with advanced or metastatic urothelial (bladder) cancer who have an FGFR3 genetic change, compared with placebo.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment450 (estimated)
Ages18 Years and up
SexAll
SponsorEli Lilly and Company Industry-sponsored
Drugs / interventionsenfortumab, pembrolizumab, vepugratinib
Locations281 sites (Huntsville, Alabama and 280 other locations)
Trial IDNCT07218380 on ClinicalTrials.gov

What this trial studies

This Phase 3, randomized, placebo-controlled trial enrolls people with unresectable locally advanced or metastatic urothelial carcinoma who have a qualifying FGFR3 genetic alteration. Participants receive either vepugratinib or placebo in combination with enfortumab vedotin and pembrolizumab, with treatment and follow-up lasting up to about six years. Key eligibility includes measurable disease by RECIST v1.1, ECOG performance status 0–2, and adequate laboratory function, and participants must be systemic-therapy–naïve for metastatic disease. The trial compares safety and anti-tumor activity of the combination versus the same regimen with placebo to determine whether adding vepugratinib improves outcomes.

Who should consider this trial

Good fit: Adults with unresectable locally advanced or metastatic urothelial carcinoma who have a qualifying FGFR3 alteration, measurable disease, ECOG 0–2, adequate labs, and no prior systemic therapy for metastatic disease are ideal candidates.

Not a fit: Patients without an FGFR3 alteration, those with prior systemic therapy for metastatic urothelial cancer, or those with small cell/neuroendocrine predominant histology or poor performance status are unlikely to benefit from enrollment.

Why it matters

Potential benefit: If successful, adding vepugratinib could slow tumor growth and extend the time patients with FGFR3‑altered advanced urothelial cancer live without disease progression compared with the regimen without it.

How similar studies have performed: Other selective FGFR inhibitors (for example erdafitinib) have shown benefit in FGFR3‑altered urothelial cancer, but combining an FGFR inhibitor with enfortumab vedotin and pembrolizumab is a newer approach with limited prior data.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Huntsville, Alabama and 280 other locations

+231 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Carcinoma, Transitional CellUrinary Bladder NeoplasmsNeoplasm MetastasisFGFR3Advanced Urothelial CarcinomaMetastatic Urothelial Carcinoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.