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.