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Vepugratinib

Phase 3

Carcinoma, Transitional Cell | Small molecule | Oncology |Eli Lilly and Company|Last Updated: Aug 21, 2026

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment450

FDA Designations

No designations recorded

Clinical trial landscape

Vepugratinib · 2 trials · 4 indications

Phase 3 1Phase 1 1
NCT07218380A Study of Vepugratinib (LY3866288) in Participants With Cancer in the Urinary TractCarcinoma, Transitional Cell
RECRUITING450 Analytics
PHASE3RECRUITING
A Study of Vepugratinib (LY3866288) in Participants With Cancer in the Urinary Tract
Carcinoma, Transitional CellUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of participants with treatment-related adverse events related to vepugratinib in combination with EV and pembrolizumab
From baseline up to 90 months
Safety Lead-in: Overall Response Rate (ORR)
From baseline up to 90 months

ORR by Investigator Assessment.

Progression-free Survival (PFS)
Baseline to Study Completion (estimated as 6 years)

PFS by blinded independent committee review (BICR).

Overall Response Rate (ORR)
Up to Approximately 30 Months or 2.5 Years
Pharmacokinetics (PK) of Vepugratinib: Area Under the Concentration versus Time Curve (AUC)
Up to 2 Months
PK of Midazolam, Rosuvastatin, and Digoxin Administered Alone and in the Presence of Vepugratinib: Area Under the Concentration versus Time Curve (AUC[0-inf])
Up to 2 Months
Complete Response Rate (CRR) in Participants with Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer (LG IR NMIBC)
Up to approximately 24 months or 5 years

Secondary Endpoints

Safety Lead-in: Disease Control Rate (DCR)
From baseline up to the end of Cycle 2 (each Cycle is 21 days)
Safety Lead-in: Time to Response (TTR)
From baseline up to 90 months
Overall Survival (OS)
Baseline to Study Completion (estimated as 6 years)
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Vepugratinib + EV + Pembrolizumab (Safety Lead In)EXPERIMENTALVepugratinib administered orally with EV + pembrolizumab administered IV
Vepugratinib + Enfortumab Vedotin (EV) + PembrolizumabEXPERIMENTALVepugratinib administered orally, and EV + pembrolizumab administered by intravenous (IV) infusion.
Placebo + EV + PembrolizumabPLACEBO_COMPARATORPlacebo administered orally, and EV + pembrolizumab administered by IV infusion.
Phase 1a: Cohort A1 Vepugratinib Monotherapy Dose EscalationEXPERIMENTALVepugratinib administered orally
Phase 1a: Cohort A2 Vepugratinib Monotherapy Dose OptimizationEXPERIMENTALVepugratinib administered orally
Phase 1b: Cohort B1, B2, B4, C1, and D1 Vepugratinib Monotherapy Dose ExpansionEXPERIMENTALVepugratinib administered orally
Phase 1b: Cohort B5 Vepugratinib Plus Pembrolizumab Plus Enfortumab VedotinEXPERIMENTALVepugratinib administered orally in combination with pembrolizumab administered IV and enfortumab vedotin administered IV
Phase 1b: MIBC Cohort B6 Vepugratinib Plus Pembrolizumab Plus Enfortumab VedotinEXPERIMENTALVepugratinib administered orally in combination with pembrolizumab administered IV and enfortumab vedotin administered IV
Experimental: Phase 1b: Cohort B7 Vepugratinib Plus Trastuzumab DeruxtecanEXPERIMENTALVepugratinib administered orally in combination with trastuzumab deruxtecan administered IV
Phase 1b: NMIBC Cohort B8 Vepugratinib Monotherapy Dose ExpansionEXPERIMENTALVepugratinib administered orally
Phase 1b: Cohort D2 (Drug to Drug Interaction)EXPERIMENTALVepugratinib Plus Midazolam Plus Digoxin Plus Rosuvastatin (Lead-In Only) followed by Vepugratinib Monotherapy Vepugratinib administered orally Midazolam with digoxin with rosuvastatin administered orally once per cycle for 2 cycles.

Interventions

NameTypeDescription
VepugratinibDRUGAdministered orally
PlaceboOTHERAdministered orally
EVDRUGAdministered by IV infusion
PembrolizumabDRUGAdministered by IV infusion
enfortumab vedotinDRUGIV
Trastuzumab DeruxtecanDRUGIV
MidazolamDRUGOral
DigoxinDRUGOral
RosuvastatinDRUGOral
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites290

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 facto...

Countries:United StatesAustraliaBrazilCanadaChinaCzechiaDenmarkFranceGermanyHungaryItalyJapanNetherlandsPolandSouth KoreaSpainTaiwanTurkey (Türkiye)United KingdomIsraelNorway
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Recent Changes (Last 90 Days)

LOWAug 21, 2026NCT07218380lastUpdatePostDate: changed
LOWAug 21, 2026NCT07218380lastUpdatePostDate: changed
MEDIUMAug 20, 2026NCT05614739Enrollment: 535 → 677
MEDIUMAug 20, 2026NCT05614739Enrollment: 535 → 677
LOWAug 17, 2026NCT07218380lastUpdatePostDate: changed
LOWAug 17, 2026NCT07218380lastUpdatePostDate: changed
LOWJul 13, 2026NCT07218380lastUpdatePostDate: changed
LOWJul 13, 2026NCT07218380lastUpdatePostDate: changed
LOWJul 7, 2026NCT07218380lastUpdatePostDate: changed
LOWJul 7, 2026NCT07218380lastUpdatePostDate: changed
LOWJun 23, 2026NCT07218380lastUpdatePostDate: changed
LOWJun 23, 2026NCT07218380lastUpdatePostDate: changed

Frequently asked questions about Vepugratinib

What is Vepugratinib used for?

Vepugratinib is an investigational small molecule being studied for the treatment of transitional cell carcinoma, urinary bladder neoplasms, and other cancers of the urinary tract, including cases with metastasis. It is currently in Phase 3 clinical development for these oncology indications.

What does Vepugratinib target?

Vepugratinib is a kinase inhibitor, a type of targeted therapy that blocks specific enzymes involved in cancer cell growth. It is being studied in patients whose tumors have alterations in the FGFR3 gene, as part of the FORAGER-1 clinical trial.

Who is developing Vepugratinib?

Vepugratinib is being developed by Eli Lilly and Company, a biopharmaceutical company traded on the stock exchange under the ticker symbol LLY. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with urinary tract cancers.

What phase is Vepugratinib in?

Vepugratinib is currently in Phase 3 clinical development. It is an investigational drug, meaning it has not yet been approved by regulatory authorities. The Phase 3 trial is actively recruiting participants to study its effects in patients with transitional cell carcinoma and related urinary tract cancers.

What clinical trials is Vepugratinib in?

Vepugratinib is being studied in two active clinical trials. The first is NCT05614739, a Phase 1 study called FORAGER-1, which is recruiting patients with FGFR3 gene alterations. The second is NCT07218380, a Phase 3 study in patients with urinary tract cancers. Both trials are currently recruiting participants.

Is Vepugratinib the same as LY3866288 or LOXO-435?

Yes, Vepugratinib is also known by the alternative names LY3866288 and LOXO-435. These names refer to the same investigational drug being developed by Eli Lilly and Company for the treatment of urinary tract cancers, including transitional cell carcinoma and bladder neoplasms.