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Recruiting

NCT Number: NCT07218380

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

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 or placebo will be administered in combination with enfortumab vedotin and pembrolizumab.

Study participation could last up to approximately 6 years.

Recruiting

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Key information

Conditions

Carcinoma, Transitional Cell Carcinoma Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Male Urogenital Diseases Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Neoplastic Processes Pathologic Processes Pathological Conditions, Signs and Symptoms Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Box Hill Hospital, Box Hill, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Vepugratinib

Drug

Administered orally

Placebo

Other

Administered orally

EV

Drug

Administered by IV infusion

Pembrolizumab

Drug

Administered by IV infusion

Primary outcomes

  1. Number of participants with treatment-related adverse events related to vepugratinib in combination with EV and pembrolizumab

    Time frame: From baseline up to 90 months

  2. Safety Lead-in: Overall Response Rate (ORR)

    Time frame: From baseline up to 90 months

    ORR by Investigator Assessment.

  3. Progression-free Survival (PFS)

    Time frame: Baseline to Study Completion (estimated as 6 years)

    PFS by blinded independent committee review (BICR).

Secondary outcomes

  1. Safety Lead-in: Disease Control Rate (DCR)

    Time frame: From baseline up to the end of Cycle 2 (each Cycle is 21 days)

    DCR by investigator assessment.

  2. Safety Lead-in: Time to Response (TTR)

    Time frame: From baseline up to 90 months

    TTR by investigator assessment.

  3. Overall Survival (OS)

    Time frame: Baseline to Study Completion (estimated as 6 years)

  4. Objective Response Rate (ORR) by BICR

    Time frame: Baseline to Study Completion (estimated as 6 years)

  5. Duration of Response (DoR)

    Time frame: Baseline to Study Completion (estimated as 6 years)

    DOR by BICR.

  6. Progression-free Survival (PFS)

    Time frame: Baseline to Study Completion (estimated as 6 years)

    PFS by investigator assessment.

  7. Objective Response Rate (ORR)

    Time frame: Baseline to Study Completion (estimated as 6 years)

    Percentage of Participants who Achieve a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR)ORR by investigator assessment

  8. Duration of Response (DOR)

    Time frame: Baseline to Study Completion (estimated as 6 years)

    DOR by investigator assessment.

  9. Progression-free Survival 2 (PFS2)

    Time frame: Baseline to Study Completion (estimated as 6 years)

    PFS2 by investigator assessment.

  10. Plasma Concentrations of Vepugratinib

    Time frame: Cycle 1 Day 1 to Study completion (estimated as 90 months)

    PK samples are to be drawn every odd cycle while participant on study.

  11. Change from Baseline in Global Health Status/Quality of Life (QOL) and Physical Function Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)

    Time frame: Baseline to Study Completion (estimated as 6 years)

    The EORTC QLQ-C30 is a validated self-reported general cancer questionnaire consisting of 30 items with a recall of the past 7 days. Response options range from 1) "very poor" to 7) "excellent." Higher scores represent better overall HRQoL.

Study contacts

Contact information is provided by the study sponsor or research team.

Physicians interested in becoming principal investigators please contact

CONTACT

[email protected]

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

CONTACT

[email protected]

1-317-615-4559

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

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

Acronym: FORAGER-2

Important dates

Study start
2025
Primary completion
2029
Study completion
2033
First posted
Oct 20, 2025
Registry last updated
Jul 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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