FORAGER-1: A Phase 1, Open-Label, Multicenter Study of Vepugratinib (LY3866288; LOXO-435) in Locally Advanced or Metastatic Solid Tumors Including Urothelial Cancer and Muscle Invasive Bladder Cancer With FGFR3 Alterations

Study Identifier:
LOXO-FG3-22001 (J4G-OX-JZVA)
CT.gov Identifier:
NCT05614739
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
2022-502755-59-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruiting

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Study Summary

The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435.

The study will be conducted in 2 phases:

Dose escalation (1a) and dose expansion (1b).

Phase 1a will assess safety, tolerability, and pharmacokinetics of LOXO-435 to determine the recommended phase 2 dose (RP2D).

Phase 1b will include 4 dose expansion cohorts of patients with prespecified activating FGFR3 alterations to evaluate the efficacy and safety of LOXO-435 at the RP2D.

Cohort B will enroll pts with mUC and includes three cohorts to evaluate LOXO-435 as monotherapy (B1, B2) and in combination with pembrolizumab (B3).

Cohort C will enroll pts with non-UC advanced solid tumors and includes a cohort to evaluate LOXO-435 as monotherapy (C1).

To evaluate LOXO-435 in patients with cancer.

To report initial clinical data from the phase 1 dose escalation cohort of LY3866288 in FGFR3-altered advanced solid tumors.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Bladder
Metastatic Cancer
Ureteral
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Participant Group/Arm Intervention/Treatment Experimental: Phase 1a: Cohort A1 Vepugratinib Monotherapy Dose Escalation
Read More
Drug: ASCO 2025 patients (pts) were treated at 10 dose levels (DLs) of LY3866288 (6 mg QD - 400 mg BID). Dose escalation used a single-patient accelerated design followed by mTPI-2 method. Adults with advanced or metastatic solid tumors with an FGFR3 alteration (tumor or blood) were eligible in dose escalation (A1). Dose optimization (A2) randomized FGFR3-altered mUC into 3 DLs (200, 300, and 400 mg BID), stratified by prior FGFRi treatment. LY plus EV and pembrolizumab (EVP) is being studied in 1L mUC (B5).
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
Inclusion criteria
  • Cohort A1, C1, D1, and D2: Locally advanced or metastatic solid tumor malignancy with a qualifying FGFR3 alteration.
  • Cohort A2, B2, B5 and B7: Urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration.
  • Cohorts B1 and B4: Urothelial cancer that is locally advanced or metastatic and have received prior erdafitinib.
  • Cohort B6: Muscle Invasive Bladder Cancer with a qualifying FGFR3 alteration.
  • Cohort B7: Urothelial cancer that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration and expression of human epidermal growth factor receptor 2 (HER2).
  • Cohort B8: Low Grade Intermediate Risk Non-Muscle Invasive Bladder cancer and a qualifying FGFR3 genetic alteration.
  • Measurability of disease:
  • Cohort A1, D1, and D2: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1).
  • Cohorts A2, B1, B2, B4, B5, B7, and C1: Measurable disease required as defined by RECIST v1.1.
  • Cohort B8: Baseline disease which includes at least 1 lesion.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of:
  • 0 or 1 for Cohorts A1, A2, B5, B6, B7, and B8.
  • Less than or equal to 2 for Cohorts B1, B2, B4, C1, DI and D2.
  • Cohort B6: Must be eligible for radical cystectomy plus pelvic lymph node dissection and agree to undergo curative intent standard radical cystectomy plus pelvic lymph node dissection.
Exclusion criteria
  • Participants with primary central nervous system (CNS) malignancy.
  • Untreated or uncontrolled CNS metastases.
  • Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible.
  • Any serious unresolved toxicities from prior therapy.
  • Significant cardiovascular disease.
  • Prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF).
  • Active uncontrolled systemic infection or other clinically significant medical conditions.
  • Participants who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment. Participants who have stopped breastfeeding may be enrolled.
  • Cohort D1 only:
  • Have had renal transplantation.
  • Have a known history of nephrotic syndrome.
  • Have uncontrolled fluid overload, including clinically significant ascites, pleural effusion, or peripheral edema.
  • Have uncontrolled hypertension.
  • Are on hemodialysis or similar.
  • Cohort D2 only:
  • Have a history of:
  • Ventricular tachycardia or ventricular fibrillation.
  • Hypertrophic obstructive cardiomyopathy unless managed concurrently with atrial fibrillation.
  • Wolff-Parkinson-White syndrome.
  • Second- or third-degree atrioventricular block unless a functioning pacemaker is in place.
  • Heart rate less than (<) 50 bpm.
  • Have any of these medical conditions:
  • Severe respiratory insufficiency.
  • Sleep apnea syndrome.
  • Myasthenia gravis.
  • Acute narrow-angle glaucoma.
  • Active liver disease or clinically significant hepatic impairment.
  • History of myopathy or rhabdomyolysis with any HMG-CoA reductase inhibitor.

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Carolinas
Myrtle Beach, SC, United States, 29572
Investigator
Neal Shore
Status
Recruiting
Condition(s) Treated at Site
Bladder
Metastatic Cancer
Ureteral