study to evaluate the safety, pharmacokinetics, and pharmacodynamics of jnj-42756493 (erdafitinib) in participants with advanced hepatocellular carcinoma

Conditions: Carcinoma, Hepatocellular

Summary: the purpose of this study is to determine recommended phase 2 dose \[rp2d\]) and the objective response rate of jnj-42756493 (erdafitinib) in advanced hepatocellular carcinoma (hcc) participants with fibroblast growth factor (fgf) 19 amplification.

this is an open-label (all people know the identity of the intervention), multicenter (when more than one hospital or medical school team work on a medical research study), 2 parts (first, dose escalation phase and second, dose expansion phase) study to evaluate the safety, pharmacokinetics, pharmacodynamics, and clinical responses of jnj-42756493 (erdafitinib) in asian participants with advanced hcc. the duration of study will be approximately 11 months per participant. the study consists of 2 periods: screening (28 days before study commences on day 1); open-label treatment (dose escalation portion of the trial \[part 1\]), participants are enrolled into cohorts at increasing dose levels of jnj-42756493 (erdafitinib) in 28 day treatment cycles. part 2, the cohort expansion part of the trial, will further explore the recommended phase 2 dose (rp2d) of jnj-42756493 (erdafitinib) as determined in part 1; and follow-up phase (up to 6 months). blood samples will be collected for evaluation of safety, pharmacokinetics, pharmacodynamics, and predictive biomarkers at pre-dose and post-dose of study treatment. recommended phase 2 dose (rp2d) for jnj-42756493 (erdafitinib) will be evaluated primarily. participants' safety will be monitored throughout the study.

Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed hepatocellular carcinoma (hcc). (histology or cytology from prior tumor biopsy specimen is acceptable). for part 1 continuous dosing regimen and part 2, hcc participants must have fibroblast growth factor (fgf) 19 amplification based on central laboratory results * participant must have advanced disease and meet all the following criteria: disease progression after previous surgical or local-regional therapy, if any; disease ineligible for surgical or local-regional therapy or systemic therapy; received no more than 1 line of systemic therapy (participants who are intolerant to previous systemic therapy are allowed.) * cirrhotic status of child-pugh class a: participants with child-pugh class b score of 7 may be considered in part 2 if no pharmacokinetic (pk) and safety issues are identified in part 1 from subjects with child-pugh class a * eastern cooperative oncology group (ecog) performance status score 0 or 1 * participants with adequate bone marrow, liver, renal function, and electrolytes according to protocol-defined criteria within the 14 days before the first dose of study drug * negative pregnancy test (urine or serum beta human chorionic gonadotropin \[beta (b)-hcg\]) at screening for women of child bearing potential who are sexually active exclusion criteria: * received systemic chemotherapy, targeted therapies, definitive radiotherapy, or treatment with an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and mitomycin c, within 6 weeks; in the case of immunotherapy, within 4 weeks) before the first administration of study drug * prior liver transplant * known fibrolamellar hcc or mixed cholangiocarcinoma and hcc * clinically active serious infections greater than (\>) common terminology criteria for adverse events (aes) grade 2 * participants with persistent calcium or phosphate \> upper limits of normal (uln) during screening (within 14 days prior to day 1 of cycle 1 up until pre-dose of cycle 1) and despite medical management of calcium or phosphate levels

Keywords: carcinoma, hepatocellular jnj 42756493 a pan-fibroblast growth factor receptor tyrosine kinase inhibitor