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A Phase 1 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 or Refractory Solid Tumors or Lymphoma

Phase 1
18 Years
Open (Enrolling)
Advanced or Refractory Solid Tumors or Lymphoma

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Trial Information

A Phase 1 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 or Refractory Solid Tumors or Lymphoma

This is a Phase 1 first-in-human, non-randomized (individuals will not be assigned by chance
to study treatments), open-label (individuals will know the identity of study treatments),
multicenter, 2-part, dose-escalation study to evaluate the safety, pharmacokinetics (study
of what the body does to a drug), and pharmacodynamics (study of what a drug does to the
body) of JNJ-42756493 administered orally to patients with advanced or refractory solid
malignancies or lymphoma who are not candidates for approved or available therapies. Each
cycle will consist of 21 days of daily continuous dosing. Part 1 is the dose-escalation
phase, which will be guided by pharmacokinetics and safety. Three to 6 new patients will be
enrolled in sequential cohorts (first cohort will receive the starting dose and subsequent
cohorts will receive increased doses of JNJ-42756493). Enrollment in each cohort will be
staggered; the second and third patient in every cohort will not be dosed until the first
patient in that cohort is beyond Day 7 of Cycle 1. If no dose-limiting toxicities (DLTs)
have been observed during the first week of Cycle 1 in the first patient, the second and
third patient in the cohort will initiate treatment. After the last patients in each cohort
completes Cycle 1 (DLT observation period of 21 days of treatment), the Safety Evaluation
Team (SET) will evaluate the safety for DLT determination and the pharmacokinetic data and
make the decision whether to escalate the dose in a new cohort of 3 to 6 new patients. Dose
escalation will halt when the maximum tolerated dose (MTD) or when the plasma concentrations
exceed the predefined cardiovascular threshold. The total number of patients to be enrolled
in Part 1 will depend on the dose level at which either the DLT or the cardiovascular safety
threshold of JNJ-42756493 will be achieved. The recommended Part 2 dose will be determined
at the end of the dose-escalation phase. Part 2 is the dose-expansion phase; approximately
12 patients will be treated at the recommended Part 2 dose to confirm FGFR target modulation
in tumor, to further expand the information of the safety, pharmacokinetics, and
pharmacodynamics of JNJ-42756493, as well as to seek any evidence of preliminary clinical
responses. Serial pharmacokinetic and pharmacodynamic samples will be collected at each
treatment cycle, and safety will be monitored throughout the study.

Inclusion Criteria:

- Histologically or cytologically confirmed solid malignancy or lymphoma that is
metastatic or unresectable, and for which standard curative treatment is no longer

- Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1

- Adequate bone marrow, liver, and renal function within the 7 days preceding the first
dose of study drug (glomerular filtration rate [GFR] will be used when GFR and serum
creatinine disagree each other)

- Serum electrolyte levels (magnesium, potassium) within institutional normal limits
(within 7 days of treatment)

- For the expansion phase, participants must have tumors that are K-ras wild-type and
also express FGFR 1, 2, or 4 gene amplifications

Exclusion Criteria:

- History or current condition of uncontrolled cardiovascular disease

- Persistent calcium or phosphate >upper limit of normal (ULN) during screening (within
7 days of treatment) and despite medical management of calcium or phosphate levels

- Patients taking medications known to have a risk of causing QTc prolongation and
Torsades de Pointes or known as strong CYP3A inhibitors or inducers

- Left ventricular ejection fraction (LVEF) <50% as assessed by echocardiography
performed at screening

- Any medical condition that requires intact wound healing capacity and is expected to
endanger patient safety if wound healing capacity would be severely reduced during
administration of the investigational agent

- History of or current clinically significant medical illness or any other illness
that the investigator considers should exclude the patient or that could interfere
with the interpretation of the study results

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Part 1 maximum tolerated dose of JNJ-42756493

Outcome Description:

The Part 1 maximum tolerated dose is the Part 2 recommended dose.

Outcome Time Frame:

Up to Part 1 Day 84 (Cycle 4, Day 21)

Safety Issue:


Principal Investigator

Janssen Research & Development, LLC Clinical Trial

Investigator Role:

Study Director

Investigator Affiliation:

Janssen Research & Development, LLC


Spain: Spanish Agency of Medicines

Study ID:




Start Date:

June 2012

Completion Date:

April 2014

Related Keywords:

  • Advanced or Refractory Solid Tumors or Lymphoma
  • Advanced or refractory solid tumors or lymphoma
  • Pharmacology
  • Pharmacokinetics
  • Pharmacodynamics
  • JNJ-42756493
  • Lymphoma
  • Neoplasms