A Phase 1, Open-label, Dose-escalation and Expansion, First-in-human Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of JBZ-001, a Dihydroorotate Dehydrogenase (DHODH) Inhibitor, in Patients With Advanced Solid and Hematological Malignancies
Summary
This will be a phase 1, open-label, dose-escalation and expansion, FIH trial to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of JBZ-001, a DHODH inhibitor, in patients with refractory solid and hematological malignancies. The study design includes two independent parts: dose escalation in solid tumors and NHL (Part 1), and up to four indication expansions in selected solid tumor types and NHL (Part 2). The dose escalation will enroll patients with solid tumors and NHL following a standard "3+3" design enrolling a minimum of 3 and up to 6 patients per dose level.
Detailed description
A phase 1, open-label, dose-escalation and expansion, FIH trial to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of JBZ-001, a DHODH inhibitor, in patients with refractory solid and hematological malignancies. The study will enroll patients with solid tumors and NHL. The study design includes two independent parts: dose escalation in solid tumors and NHL (Part 1), and up to four indication expansions in selected solid tumor types and NHL (Part 2). The dose escalation will enroll patients with solid tumors and NHL following a standard "3+3" design enrolling a minimum of 3 and up to 6 patients per dose level. Single-patient efficacy signals (i.e. CR or PR) may be followed in an efficacy-signal dose expansion cohort of up to 10 patients on any given dose level with the same tumor type. In addition to dose-limiting toxicity (DLT) evaluation during dose escalation, a Bayesian safety monitoring rule will be used to evaluate the rate of DLTs during cohort expansions. The study includes subgroup-specific eligibility criteria, DLTs, safety and efficacy monitoring, and other indication-relevant aspects. Patients with clinical benefit may be treated until disease progression or toxicity. The primary objective is to evaluate the safety and tolerability and establish an OBD of single agent JBZ-001 in patients with solid tumors and NHL. Secondary objectives include efficacy endpoints and the PK of single agent JBZ-001. To characterize the JBZ-001 single dose PK profile, the patients enrolled in the first dose level will first receive a single dose of JBZ-001 followed by one-week off-drug (Cycle 0). Exploratory objectives include correlative studies of plasma cell expression of CD38, CD47, and other markers.
Arms & interventions
- DrugJBZ-001
JBZ-001 Oral Capsule
Outcome measures
Primary
Occurrence of all adverse events
Evaluation of adverse events
Time frame: 28 Days
Maximum tolerated dose (MTD)
MTD will be defined as the maximum dose level at which no more than 1 of 3 participants experience a dose-limiting toxicity (DLT) within the first 33days of multiple dosing.
Time frame: 28 days
Phase II dose (RP2D)
The number and proportion of patients experiencing at least 1 dose-limiting toxicity (DLT) will be used as the primary measure to evaluate the RP2D
Time frame: 28 days
Secondary
Maximum plasma concentration (Cmax)
Time frame: 28 days
Time to Cmax (tmax)
Time frame: 28 days
Area under the serum concentration-time curve (AUC[0-t]
Time frame: 28 days
Area under the serum concentration-infinity curve AUC[0-infinity]
Time frame: 28 days
Apparent terminal phase half-life (t1/2)
Time frame: 28 days
Overall Response Rate (ORR)
Time frame: up to 1 year(anticipated)
Duration of response (DoR)
Time frame: up to 1 year(anticipated)
Progression-free survival (PFS)
Time frame: up to 1 year(anticipated)
Time to Progression (TTP)
Time frame: up to 1 year(anticipated)
Eligibility criteria
Study locations (2)
The Ohio State University
Columbus, Ohio, 43210
START Mountain Region
West Valley City, Utah, 84119