Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as [14C]-LY3866288, Vepugratinib, LOXO-435
LY3866288 · 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...
LY3866288 is an investigational small molecule developed by Eli Lilly and Company. It is in Phase 1 clinical development, and its therapeutic indications have not been disclosed. The program has completed two Phase 1 trials in healthy participants, with a combined enrollment of 30 people.
LY3866288 targets FGFR3, a receptor tyrosine kinase. FGFR3 is a receptor in the fibroblast growth factor receptor family. The drug is a small molecule designed to interact with this receptor target.
LY3866288 is developed by Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY. Lilly is the sponsor of the clinical program for this investigational small molecule.
LY3866288 is in Phase 1 clinical development. It is investigational and has not been approved by the FDA. Two Phase 1 trials have been completed, and no trials are currently active.
LY3866288 has been studied in two completed Phase 1 trials. NCT06644378 evaluated [14C]-LY3866288 in 15 healthy participants in the United States. NCT06641037 evaluated LY3866288 in 15 healthy participants, also in the United States. Both trials enrolled adults and are now completed.
Yes. [14C]-LY3866288 is an alternative name for LY3866288. The carbon-14 labeled form was used in the Phase 1 trial NCT06644378, which studied the drug in healthy participants. Searches for either name refer to the same Eli Lilly investigational compound.