Vepugratinib for Bladder Cancer

(FORAGER-2 Trial)

Recruiting at 279 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Disqualifiers: Prior systemic therapy, Neuropathy, CNS involvement, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 6 years

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine, vepugratinib, as a potential cancer treatment for individuals with advanced or metastatic bladder cancer. The study aims to determine the safety and effectiveness of vepugratinib when combined with other treatments, compared to a placebo (a harmless pill with no active drug). Participants will receive either vepugratinib or a placebo, both combined with two other treatments: enfortumab vedotin and pembrolizumab. This trial suits those with advanced bladder cancer and a specific genetic change called FGFR3. Participants should not have received prior treatment for their advanced cancer. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that vepugratinib was safe in earlier studies. Initial results from the FORAGER-1 study found that patients with advanced solid tumors, such as bladder cancer, tolerated this treatment well. Although vepugratinib remains under investigation, the data suggest it is generally safe when combined with other treatments like enfortumab vedotin and pembrolizumab.

However, it is important to remember that vepugratinib is not yet fully approved, and not all risks are known. Participants should consider this when deciding to join a clinical trial for this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Researchers are excited about Vepugratinib for bladder cancer because it offers a unique approach compared to current treatments. Unlike traditional therapies, which often involve chemotherapy or immunotherapy alone, Vepugratinib is combined with Enfortumab Vedotin (EV) and Pembrolizumab to create a powerful trio. This combination targets cancer cells more precisely by integrating an oral administration with intravenous infusions. Vepugratinib's potential to enhance the effectiveness of existing treatments makes it a promising candidate in the fight against bladder cancer.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that vepugratinib may help treat advanced bladder cancer. One study found that about one-third of patients who took vepugratinib experienced a reduction or disappearance of their cancer. This trial will test vepugratinib in combination with enfortumab vedotin and pembrolizumab, with some participants receiving this combination. Early research suggests that vepugratinib might enhance the effectiveness of these other cancer treatments. Although survival rates for advanced bladder cancer are usually low, combining vepugratinib with these treatments offers hope for better outcomes. Overall, these early findings suggest that vepugratinib could be an important addition to bladder cancer treatment options. ^{1 2 3 6 7}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for individuals with advanced or metastatic bladder cancer. Participants must meet certain health criteria to join, but specific inclusion and exclusion details are not provided in the summary given.

Inclusion Criteria

Have measurable disease by investigator assessment defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Have adequate laboratory parameters

My cancer has a specific genetic change in FGFR3.

Exclusion Criteria

I don't have any serious side effects from previous cancer treatments.

I have moderate to severe numbness, tingling, or muscle weakness.

I have not treated or controlled brain involvement or any history of disease in the lining of my brain and spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Participants receive vepugratinib or placebo in combination with standard of care therapy to assess safety and initial response

Up to 90 months

Treatment

Participants continue receiving vepugratinib or placebo with standard of care therapy to evaluate efficacy and safety

Up to 6 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vepugratinib

Trial Overview

The study tests vepugratinib against a placebo alongside standard of care therapies to evaluate its safety and effectiveness in treating bladder cancer over a period that could last up to 6 years.

How Is the Trial Designed?

Group I: Vepugratinib + Enfortumab Vedotin (EV) + Pembrolizumab Experimental Treatment 3 Interventions

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

Group II: Vepugratinib + EV + Pembrolizumab (Safety Lead In) Experimental Treatment 3 Interventions

Vepugratinib administered orally with EV + pembrolizumab administered IV

Group III: Placebo + EV + Pembrolizumab Placebo Group 3 Interventions

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

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Citations

1.

onclive.com

onclive.com/view/vepugratinib-based-therapy-displays-potential-in-metastatic-fgfr3-urothelial-cancer

Vepugratinib-Based Therapy Displays Potential ... - OncLive

Data presented at the 2025 ESMO Congress demonstrated that vepugratinib yielded an overall response rate of 34% when given at 200 mg twice per ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07218380

NCT07218380 | A Study of Vepugratinib (LY3866288) in ...

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 ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12025360/

Real-World Clinical Outcomes with First-Line Systemic ...

Patients with locally advanced or metastatic urothelial cancer (la/mUC) have poor prognosis, with an estimated 5-year survival rate of 8.8% [2].

4.

urotoday.com

urotoday.com/conference-highlights/esmo-2025/esmo-2025-bladder-cancer/164036-esmo-2025-forager-1-a-phase-1-study-of-ly3866288-a-potent-highly-isoform-selective-fgfr3-inhibitor-in-fgfr3-altered-advanced-solid-tumors.html

ESMO 2025: FORAGER-1: A Phase 1 Study of LY3866288, ...

The initial results from the FORAGER-1 study showed a favorable safety profile and promising antitumor activity in patients with previously ...

5.

oncologynewscentral.com

oncologynewscentral.com/bladder-cancer/huge-difference-in-overall-survival-shown-in-new-real-world-bladder-cancer-data

Dramatic Improvement in Overall Survival Shown in New ...

The study, which was published in JAMA Network Open, demonstrated a contemporary survival probability of nearly 30% at three years. “I think ...

6.

ctv.veeva.com

ctv.veeva.com/study/a-study-of-vepugratinib-ly3866288-in-participants-with-cancer-in-the-urinary-tract

A Study of Vepugratinib (LY3866288) in Participants With ...

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 ...

7.

lillyoncologypipeline.com

lillyoncologypipeline.com/plain-language-summaries/VepugratinibFGFR3PLTRUpdateJuly2025.pdf

Vepugratinib FGFR3 PLTR Update July 2025

The use of vepugratinib is experimental. Not all risks are known. There is no guarantee that a participant's cancer will improve when taking part in this study.