A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies

Study Overview
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Brief Summary
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The study will determine the maximum tolerated dose and thus the recommended phase II dose and schedule of the compound and characterize the safety.

Official Title
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A Phase I, Open-label, Multi-center, Dose Escalation Study of Oral BGJ398, a Pan FGF-R Kinase Inhibitor, in Adult Patients With Advanced Solid Malignancies

Conditions
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Advanced Solid Tumors With Alterations of FGFR1, 2 and or 3, Squamous Lung Cancer With FGFR1 Amplification, Bladder Cancer With FGFR3 Mutation or Fusion, Advanced Solid Tumors With FGFR1 Amplication, Advanced Solid Tumors With FGFR2 Amplication, Advanced Solid Tumors With FGFR3 Mutation

Intervention / Treatment
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* Drug: BGJ398


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically/cytologically confirmed advanced solid tumors with FGFR1 or FGFR2 amplification or FGFR3 mutation, for which no further effective standard anticancer treatment exists Adequate bone marrow function Adequate hepatic and renal function Adequate cardiovascular function Contraception. For women: Must be surgically sterile, post-menopausal, or compliant with a medically approved contraceptive regimen during and for 3 months after the treatment period; must have a negative serum or urine pregnancy test and must not be nursing. For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 3 months after the treatment period Exclusion Criteria: Patients with primary CNS tumor or CNS tumor involvement Patients with history and/or current evidence of endocrine alteration of calcium-phosphate homeostasis History and/or current evidence of ectopic mineralization/ calcification including but not limited to the soft tissue, kidneys, intestine, myocard and lung with the exception of calcified lymphnodes and asymptomatic coronary calcification Current evidence of corneal disorder/ keratopathy incl. but not limited to bullous/ band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis etc., confirmed by ophthalmologic examination. History or current evidence of cardiac arrhythmia and/or conduction abnormality Women who are pregnant or nursing. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BGJ398<br> | Drug: BGJ398<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate and category of dose-limiting toxicities will be tabulated for patients included in the dose escalation portion of the study, to establish the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPTD) | Incidence rate and category of dose-limiting toxicities will be tabulated for patients included in the dose escalation portion of the study, to establish the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPTD). This will be calculated using an established statistical model, based on incidence of adverse events and serious adverse events, physical examinations, vital signs, electrocardiograms, and laboratory parameters | 23 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess preliminary anti-tumor activity of BGJ398 for patients in expansion Arm 4 (previously treated patients with advanced/metastatic UCC with FGFR3 gene alterations) | overall response rate (ORR), as assessed by investigator per RECIST v 1.0; overall survival (OS), duration of response (DOR) and disease control rate (DCR) will be assessed | 23 months | 
| To determine the pharmacokinetic (PK) profiles of oral BGJ398 | Time vs. concentration profiles, PK parameters of BGJ398 and known active metabolite(s). | 23 months | 
| To evaluate the pharmacodynamic effect of the drug. | Pre- vs. post treatment serial changes in FGF23 plasma levels (not done for patients enrolled to expansion Arm 4) | 23 months | 
| Assess preliminary anti-tumor activity for patients not in Arm 4. | Overall tumor response rate (ORR) and PFS assessed by investigator per RECIST | 23 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced solid tumors, lung cancer, bladder cancer, BGJ398, FGFR, kinase inhibitor, advanced solid malignancies