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Vepugratinib

Phase 3

Carcinoma, Transitional Cell | Small molecule | Oncology |Eli Lilly and Company|Trials Updated: Oct 8, 2026

Vepugratinib development status

Highest phase Phase 3
Registered trials 6 across 1 sponsor since Nov 2022

Vepugratinib target and mechanism

Target class-Tinib (Kinase)
ModalitySmall molecule

Also known as LY3866288, LOXO-435

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials5
Total Enrollment1,318

FDA Designations

No designations recorded

Vepugratinib clinical trials

Vepugratinib · 5 trials · 7 indications

Phase 3 1Phase 2 1Phase 1 3
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).

Number of Participants with LG IR NMIBC with Complete Response
Baseline, 2 Years

Complete response rate is defined as negative cystoscopy and negative cytology .

Number of Participants with LG UTUC with Complete Response
Baseline, 2 Years

Complete response rate is defined as negative uterorenoscopy or nephroscopy assessment and negative cytology, per investigator assessment.

Part A, Fraction of [14C]-LY3866288 Dose Excreted in Urine (Feur) Expressed as a Percentage of the Total Radioactive Dose Administered
Predose up to Day 21 postdose
Part A, Fraction of Dose [14C]-LY3866288 Excreted in Feces Expressed as a Percentage of the Total Radioactive Dose Administered
Predose up to Day 21 postdose
Part B, Absolute Bioavailability (Fabs) of LY3866288
Predose up to Day 9 postdose
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration of LY3866288
Baseline to Study Completion (Up to 3 Weeks)

PK: AUC From Time 0 to the Time of the Last Quantifiable Concentration of LY3866288

PK: AUC Extrapolated to Infinity of LY3866288
Baseline to Study Completion (Up to 3 Weeks)
PK: Maximum Concentration (Cmax) of LY3866288
Baseline to Study Completion (Up to 3 Weeks)

PK: Cmax of LY3866288

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.
Cohort A: VepugratinibEXPERIMENTALVepugratinib will be administered orally to participants with low-grade intermediate-risk non-muscle invasive bladder cancer (LG IR NMIBC)
Cohort B: VepugratinibEXPERIMENTALVepugratinib will be administered orally to participants with low-grade upper tract urothelial carcinoma (LG UTUC)
Part A: [14C]-LY3866288EXPERIMENTALSingle dose of \[¹⁴C\]-LY3866288 administered orally.
Part B: LY3866288 + [14C]-LY3866288EXPERIMENTALSingle dose of LY3866288 administered orally followed by a single dose of \[¹⁴C\]-LY3866288 administered intravenously (IV).
LY3866288 Cohort 1 (High-Fat Meal)EXPERIMENTALLY3866288 single and multiple capsules administered orally under fasted/fed conditions in cross-over manner within cohort
LY3866288 Cohort 2 (Low-Fat Meal)EXPERIMENTALLY3866288 single and multiple capsules administered orally under fasted/fed conditions in cross-over manner within cohort
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
[14C]-LY3866288DRUGAdministered orally.
LY3866288DRUGAdministered orally.
enfortumab vedotinDRUGIV
Trastuzumab DeruxtecanDRUGIV
MidazolamDRUGOral
DigoxinDRUGOral
RosuvastatinDRUGOral
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites276

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)

LOWOct 8, 2026NCT07827612lastUpdatePostDate: changed
LOWOct 8, 2026NCT07827612lastUpdatePostDate: changed
LOWOct 7, 2026NCT07218380lastUpdatePostDate: changed
LOWOct 7, 2026NCT07218380lastUpdatePostDate: changed
LOWSep 22, 2026NCT07218380lastUpdatePostDate: changed
LOWSep 22, 2026NCT07218380lastUpdatePostDate: changed
LOWSep 19, 2026NCT07827612NEW_TRIAL: changed
LOWSep 19, 2026NCT07827612NEW_TRIAL: changed
LOWSep 19, 2026NCT07827612NEW_TRIAL: changed
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

Frequently asked questions about Vepugratinib

What is Vepugratinib?

Vepugratinib is an investigational small molecule kinase inhibitor being developed by Eli Lilly and Company for the treatment of urinary tract cancers, including transitional cell carcinoma and urinary bladder neoplasms. It is currently in Phase 3 clinical development and is designed to target cancers with specific genetic alterations.

What is Vepugratinib used for in bladder cancer?

Vepugratinib is being studied for use in patients with urinary bladder neoplasms and other urinary tract cancers, including non-muscle invasive bladder cancer, upper tract urothelial cancer, and metastatic transitional cell carcinoma. It is an investigational therapy and has not been approved for any indication.

What does Vepugratinib target?

Vepugratinib targets FGFR3, a fibroblast growth factor receptor kinase. It is a small molecule kinase inhibitor that selectively inhibits FGFR3, and it is being evaluated in biomarker-selected patients whose tumors have FGFR3 alterations.

Who is developing Vepugratinib?

Vepugratinib is being developed by Eli Lilly and Company (ticker: LLY). The drug, also known as LY3866288, is part of Lilly's oncology pipeline and is currently in Phase 3 clinical trials.

What phase is Vepugratinib in?

Vepugratinib is in Phase 3 clinical development. It is an investigational drug and has not been approved by the FDA or any other regulatory agency. Two active trials are ongoing, including a Phase 3 study and a Phase 2 study.

What clinical trials is Vepugratinib in?

Vepugratinib is being evaluated in three clinical trials: the Phase 3 NCT07218380 study in urinary tract cancers, the Phase 2 NCT07827612 study in non-muscle invasive bladder cancer and upper tract urothelial cancer, and the Phase 1 FORAGER-1 trial, NCT05614739, in FGFR3-altered cancers.

Is Vepugratinib the same as LOXO-435?

Yes, Vepugratinib is also known as LOXO-435 and LY3866288. These names refer to the same investigational drug candidate developed by Eli Lilly and Company.