A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies
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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.
Condition or disease
Advanced Solid Tumors With Alterations of FGFR1, 2 and or 3Squamous Lung Cancer With FGFR1 AmplificationBladder Cancer With FGFR3 Mutation or FusionAdvanced Solid Tumors With FGFR1 AmplicationAdvanced Solid Tumors With FGFR2 AmplicationAdvanced Solid Tumors With FGFR3 Mutation
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) [ Time Frame: 23 months ]
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
Secondary Outcome Measures
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) [ Time Frame: 23 months ]
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
To determine the pharmacokinetic (PK) profiles of oral BGJ398 [ Time Frame: 23 months ]
Time vs. concentration profiles, PK parameters of BGJ398 and known active metabolite(s).
To evaluate the pharmacodynamic effect of the drug. [ Time Frame: 23 months ]
Pre- vs. post treatment serial changes in FGF23 plasma levels (not done for patients enrolled to expansion Arm 4)
Assess preliminary anti-tumor activity for patients not in Arm 4. [ Time Frame: 23 months ]
Overall tumor response rate (ORR) and PFS assessed by investigator per RECIST
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Ages Eligible for Study:
18 Years and older (Adult, Senior)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
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
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
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