Brief Summary
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of Vepugratinib by itself or when it is combined with other medicines that treat cancer. Vepugratinib may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Study participation could last up to approximately 6 years, depending on which part of the study you join.
Brief Title
FORAGER-1: A Study of Vepugratinib (LY3866288; LOXO-435) in Participants With Cancer With a Change in a Gene Called FGFR3
Detailed Description
This is an open-label, multi-center, phase 1 study in participants with FGFR3-altered advanced solid tumor malignancy including metastatic urothelial cancer (UC), muscle-invasive bladder cancer (MIBC), and low grade intermediate risk non-muscle-invasive bladder cancer (LG IR NMIBC). The study will be conducted in 2 phases. Phase 1a will assess safety, tolerability, and pharmacokinetics of Vepugratinib to determine the optimal dose for further expansion. Phase 1b will include dose expansion cohorts to evaluate the efficacy and safety of Vepugratinib as monotherapy or in combinations with other medicines that treat cancer.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-317-615-4559
Central Contact Email
LillyTrials@Lilly.com
Central Contact Role
Contact
Central Contact Email
clinical_inquiry_hub@lilly.com
Completion Date
Completion Date Type
Estimated
Conditions
URINARY BLADDER NEOPLASMS
NEOPLASM METASTASIS
URETERAL NEOPLASMS
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Keywords
Bladder Cancer
Bladder Urothelial Carcinoma
Urinary Bladder Cancer
Urinary Tract Cancer
Renal Pelvis Cancer
Ureter Cancer
Non-Muscle Invasive Bladder Cancer
Muscle Invasive Bladder Cancer
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05614739
Org Class
Industry
Org Full Name
Eli Lilly and Company
Org Study Id
18594
Overall Status
Recruiting
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
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
Primary Outcomes
Outcome Measure
Overall Response Rate (ORR)
Outcome Time Frame
Up to Approximately 30 Months or 2.5 Years
Outcome Measure
Pharmacokinetics (PK) of Vepugratinib: Area Under the Concentration versus Time Curve (AUC)
Outcome Time Frame
Up to 2 Months
Outcome Measure
PK of Midazolam, Rosuvastatin, and Digoxin Administered Alone and in the Presence of Vepugratinib: Area Under the Concentration versus Time Curve (AUC[0-inf])
Outcome Time Frame
Up to 2 Months
Outcome Measure
Complete Response Rate (CRR) in Participants with Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer (LG IR NMIBC)
Outcome Time Frame
Up to approximately 24 months or 5 years
Secondary Ids
Secondary Id
J4G-OX-JZVA
Secondary Id
2022-502755-59-00
Secondary Id
LOXO-FG3-22001
Secondary Outcomes
Outcome Time Frame
Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 3 Day 1 (28 Day Cycles)
Outcome Measure
Change from Baseline in Bladder-Related Symptoms, Measured by Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) Subscale (BlCS)
Outcome Time Frame
Up to Approximately 30 Months or 2.5 Years
Outcome Measure
Change from Baseline in Physical Function, Measured by FACT- Physical Well-Being Scale (PWB) Subscale
Outcome Time Frame
Up to approximately 30 months or 2.5 years
Outcome Measure
Event-Free Survival (EFS) in Participants with Muscle Invasive Bladder Cancer (MIBC)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Genitourinary (GU) & Urologic Cancers --- UROLOGIC NEOPLASMS
Genitourinary (GU) & Urologic Cancers --- UROGENITAL NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Kidney & Urinary Tract --- URINARY BLADDER DISEASES
Kidney & Urinary Tract --- UROLOGIC DISEASES
Cancer --- CARCINOMA
MeSH Terms
URINARY BLADDER NEOPLASMS
NEOPLASM METASTASIS
URETERAL NEOPLASMS
UROLOGIC NEOPLASMS
NON-MUSCLE INVASIVE BLADDER NEOPLASMS
UROGENITAL NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
FEMALE UROGENITAL DISEASES
FEMALE UROGENITAL DISEASES AND PREGNANCY COMPLICATIONS
UROGENITAL DISEASES
URINARY BLADDER DISEASES
UROLOGIC DISEASES
MALE UROGENITAL DISEASES
NEOPLASTIC PROCESSES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
URETERAL DISEASES
CARCINOMA
NEOPLASMS, GLANDULAR AND EPITHELIAL
NEOPLASMS BY HISTOLOGIC TYPE
PEMBROLIZUMAB
ENFORTUMAB VEDOTIN
TRASTUZUMAB DERUXTECAN
MIDAZOLAM
DIGOXIN
ROSUVASTATIN CALCIUM
BENZODIAZEPINES
BENZAZEPINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS
DIGITALIS GLYCOSIDES
CARDENOLIDES
CARDIAC GLYCOSIDES
CARDANOLIDES
STEROIDS
FUSED-RING COMPOUNDS
POLYCYCLIC COMPOUNDS
GLYCOSIDES
CARBOHYDRATES
SULFONAMIDES
AMIDES
ORGANIC CHEMICALS
FLUOROBENZENES
HYDROCARBONS, FLUORINATED
HYDROCARBONS, HALOGENATED
HYDROCARBONS
SULFONES
SULFUR COMPOUNDS
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING