Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as LY3866288, LOXO-435
Vepugratinib · 5 trials · 7 indications
ORR by Investigator Assessment.
PFS by blinded independent committee review (BICR).
Complete response rate is defined as negative cystoscopy and negative cytology .
Complete response rate is defined as negative uterorenoscopy or nephroscopy assessment and negative cytology, per investigator assessment.
PK: AUC From Time 0 to the Time of the Last Quantifiable Concentration of LY3866288
PK: Cmax of LY3866288
| Arm | Type | Description |
|---|---|---|
| Vepugratinib + EV + Pembrolizumab (Safety Lead In) | EXPERIMENTAL | Vepugratinib administered orally with EV + pembrolizumab administered IV |
| Vepugratinib + Enfortumab Vedotin (EV) + Pembrolizumab | EXPERIMENTAL | Vepugratinib administered orally, and EV + pembrolizumab administered by intravenous (IV) infusion. |
| Placebo + EV + Pembrolizumab | PLACEBO_COMPARATOR | Placebo administered orally, and EV + pembrolizumab administered by IV infusion. |
| Cohort A: Vepugratinib | EXPERIMENTAL | Vepugratinib will be administered orally to participants with low-grade intermediate-risk non-muscle invasive bladder cancer (LG IR NMIBC) |
| Cohort B: Vepugratinib | EXPERIMENTAL | Vepugratinib will be administered orally to participants with low-grade upper tract urothelial carcinoma (LG UTUC) |
| Part A: [14C]-LY3866288 | EXPERIMENTAL | Single dose of \[¹⁴C\]-LY3866288 administered orally. |
| Part B: LY3866288 + [14C]-LY3866288 | EXPERIMENTAL | Single dose of LY3866288 administered orally followed by a single dose of \[¹⁴C\]-LY3866288 administered intravenously (IV). |
| LY3866288 Cohort 1 (High-Fat Meal) | EXPERIMENTAL | LY3866288 single and multiple capsules administered orally under fasted/fed conditions in cross-over manner within cohort |
| LY3866288 Cohort 2 (Low-Fat Meal) | EXPERIMENTAL | LY3866288 single and multiple capsules administered orally under fasted/fed conditions in cross-over manner within cohort |
| Phase 1a: Cohort A1 Vepugratinib Monotherapy Dose Escalation | EXPERIMENTAL | Vepugratinib administered orally |
| Phase 1a: Cohort A2 Vepugratinib Monotherapy Dose Optimization | EXPERIMENTAL | Vepugratinib administered orally |
| Phase 1b: Cohort B1, B2, B4, C1, and D1 Vepugratinib Monotherapy Dose Expansion | EXPERIMENTAL | Vepugratinib administered orally |
| Phase 1b: Cohort B5 Vepugratinib Plus Pembrolizumab Plus Enfortumab Vedotin | EXPERIMENTAL | Vepugratinib administered orally in combination with pembrolizumab administered IV and enfortumab vedotin administered IV |
| Phase 1b: MIBC Cohort B6 Vepugratinib Plus Pembrolizumab Plus Enfortumab Vedotin | EXPERIMENTAL | Vepugratinib administered orally in combination with pembrolizumab administered IV and enfortumab vedotin administered IV |
| Experimental: Phase 1b: Cohort B7 Vepugratinib Plus Trastuzumab Deruxtecan | EXPERIMENTAL | Vepugratinib administered orally in combination with trastuzumab deruxtecan administered IV |
| Phase 1b: NMIBC Cohort B8 Vepugratinib Monotherapy Dose Expansion | EXPERIMENTAL | Vepugratinib administered orally |
| Phase 1b: Cohort D2 (Drug to Drug Interaction) | EXPERIMENTAL | Vepugratinib 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. |
| Name | Type | Description |
|---|---|---|
| Vepugratinib | DRUG | Administered orally |
| Placebo | OTHER | Administered orally |
| EV | DRUG | Administered by IV infusion |
| Pembrolizumab | DRUG | Administered by IV infusion |
| [14C]-LY3866288 | DRUG | Administered orally. |
| LY3866288 | DRUG | Administered orally. |
| enfortumab vedotin | DRUG | IV |
| Trastuzumab Deruxtecan | DRUG | IV |
| Midazolam | DRUG | Oral |
| Digoxin | DRUG | Oral |
| Rosuvastatin | DRUG | Oral |
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...
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.
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.
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.
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.
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.
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.
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.