Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-42756493 (Erdafitinib) in Participants With Advanced Hepatocellular Carcinoma

NCT02421185 | Completed Phase 1

• 2 other identifiers: CR10697142756493HCC1001
• Study Type: interventional
• Target: 53
• Locations: 3 countries
• Sites: 10

Brief 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.

Conditions

Carcinoma, Hepatocellular

Keywords

Carcinoma, Hepatocellular; JNJ 42756493; a pan-Fibroblast Growth Factor Receptor Tyrosine Kinase Inhibitor

Outcome Measures

Primary Outcomes (2)

• Part 1:Recommended Phase 2 Dose (RP2D)

  RP2D will be determined based on pharmacodynamics, biomarker response or clinical response, as well as the incidence rate and nature of the toxicities observed.

  Up to Part 1 Day 84 (Cycle 3, Day 28) (approximately 84 days)

• Number of participants with Objective Response

  Objective response based on assessment of confirmed Complete response (CR) or partial response (PR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.

  up to Month 12

Secondary Outcomes (12)

• Number of Participants With Adverse Events

  up to Month 12

• Time to Progression (TTP)

  up to Month 12

• Disease Control Rate (DCR)

  up to Month 12

• Progression-free Survival

  up to Month 12

• Maximum Observed Plasma Concentration of JNJ-42756493 (erdafitinib)

  Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)

Study Arms (1)

Part 1: Dose Escalation and Part 2: Dose Expansion

EXPERIMENTAL

Part 1: First, participants will receive 8 milligram (mg) (starting dose) tablet of JNJ-42756493 (erdafitinib) orally once daily from Day 1 to 7, then Day 15 to 21 of 28 days cycle or 8 mg orally once daily from Day 1 to 21 of 28 days cycle (intermittent dosing). After recommended Phase 2 dose (RP2D) is identified, enrollment of continuous dosing schedule will be open, starting at 8mg. In this cohort, participants will receive 8mg (starting dose) tablet of JNJ42756493 (erdafitinib) orally once daily from Day 1 to Day 28 in a 28-day cycle. Dose of the study medication will be escalated sequentially till the dose limiting toxicity is achieved to determine RP2D. Part 2: Participants will receive RP2D JNJ-42756493 (erdafitinib) dose determined in Part 1. Participants who are tolerating study drug treatment and achieve clinical responses or stable disease will continue to receive study drug at the same dose until disease progression, unacceptable toxicity, or withdrawal of consent.

Drug: JNJ-42756493 (erdafitinib)

Interventions

JNJ-42756493 (erdafitinib) DRUG

Part 1: Participants will receive 8 mg tablet once daily from Day 1 to 7, and then Day 15 to 21 of 28 days cycle or 8 mg orally once daily of 28 days cycle up to the maximum tolerated dose in order to determine the recommended Phase 2 dose. Part 2: Recommended Phase 2 JNJ-42756493 (erdafitinib) dose determined in Part 1.

Part 1: Dose Escalation and Part 2: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (10)

Unknown Facility

Changchun, China

Location

Unknown Facility

Guangzhou, China

Location

Unknown Facility

Hangzhou, China

Location

Unknown Facility

Harbin, China

Location

Unknown Facility

Nanjing, China

Location

Unknown Facility

Shanghai, China

Location

Unknown Facility

Seoul, South Korea

Location

Unknown Facility

Kaohsiung City, Taiwan

Location

Unknown Facility

Tainan, Taiwan

Location

Unknown Facility

Taipei, Taiwan

Location

Related Links

• A Phase 1/2a Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-42756493, a pan-Fibroblast Growth Factor Receptor (FGFR) Tyrosine Kinase Inhibitor, in Subjects with Advanced Hepatocellular Carcinoma (HCC)

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

erdafitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2015
• First Posted: April 20, 2015
• Study Start: May 25, 2015
• Primary Completion: May 13, 2019
• Study Completion: May 16, 2019
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

TW (3); CN (6); KR (1)