This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics, efficacy and preliminary food effect of BB102, a highly selective and potent FGFR4 inhibitor, as monotherapy in subjects with advanced solid tumors. This study has two phase: dose escalation phase and expansion phase.
This first-in-human (FIH) study of BB102 will evaluate safety, tolerability, pharmacokinetics (PK), efficacy and preliminary food effect in subjects with advanced solid tumors. In dose escalation trial, the primary objective is to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of BB102 as monotherapy, and to evaluate the safety and tolerability of BB102. The secondary objectives include the assessments of PK profile, preliminary efficacy, preliminary food effect (FE), preliminary metabolites identification, biomarkers and C-QTcF analysis of BB102. In expansion trial, the primary objective is to evaluate the efficacy of BB102 in subjects with FGF19 or FGFR4 positive advanced primary hepatocellular carcinoma (HCC) or other advanced solid tumors. The secondary objectives include the assessments of PK profile, safety and biomarkers of BB102.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
78
BB102 tablets will be administered orally once daily(QD).
Nanfang Hospital
Guangzhou, Guangdong, China
RECRUITINGHenan Cancer Hospital
Zhengzhou, Henan, China
RECRUITINGNumber of subjects with dose limiting toxicities (DLTs)
To assess the safety and tolerability of BB102 tablet as monotherapy in subjects with advanced solid tumors and to determine the maximum tolerated dose (MTD) of BB102 tablet, and to provide a basis for determination of the recommended dose (RP2D) for Phase II clinical trials.
Time frame: Single dose to the end of Cycle 1 (each cycle is 21 days)
Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
AEs and SAEs will be characterized by type, seriousness, relationship to study treatment, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 5.0) and timing. FGF19 or FGFR4 positive advanced primary HCC or other advanced solid tumors.
Time frame: From screening (Day -28 to Day -1) through up to 12 months or until disease progression
Pharmacokinetic Assessments: Peak Plasma Concentration (Cmax)
Blood samples will be collected for PK analyses
Time frame: Day 1, Day 8, Day 15 and at the end of Cycle 1 (each cycle is 21 days)
Pharmacokinetic Assessments: Time to Peak Concentration (Tmax)
Blood samples will be collected for PK analyses
Time frame: Day 1, Day 8, Day 15 and at the end of Cycle 1 (each cycle is 21 days)
Pharmacokinetic Assessments: Area under the plasma concentration-time curve (AUC)
Blood samples will be collected for PK analyses
Time frame: Day 1, Day 8, Day 15 and at the end of Cycle 1 (each cycle is 21 days)
Pharmacokinetic Assessments: Elimination half-life (t½)
Blood samples will be collected for PK analyses
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Time frame: Day 1, Day 8, Day 15 and at the end of Cycle 1 (each cycle is 21 days)
Objective response rate (ORR)
Tumor response measured by radiologic imaging techniques at baseline and throughout the study.
Time frame: From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Duration of response (DOR)
Tumor response measured by radiologic imaging techniques at baseline and throughout the study.
Time frame: From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Disease control rate (DCR)
Tumor response measured by radiologic imaging techniques at baseline and throughout the study.
Time frame: From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Progression-free survival (PFS)
Tumor response measured by radiologic imaging techniques at baseline and throughout the study.
Time frame: From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months