Trial to Evaluate the Safety & Tolerability of JBZ-001 in Pts With Advanced Solid and Hematological Malignancies

Phase 1

Recruiting

• Conditions: Solid Tumor
• Interventions: Drug: JBZ-001

• Registration Number: NCT06801002
• Lead Sponsor: Jabez Bioscience, Inc

Brief 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

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 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.

Study Timeline

• Study First Submitted: 2024-11-07
• Study First Submitted QC: 2025-01-23
• Study First Posted: 2025-01-30
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-10
• Last Update Posted: 2025-03-12
• Study Start: 2025-03-30
• Primary Completion: 2027-02-15
• Study Completion: 2028-02-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

1. Participant must be ≥18 years of age, at the time of signing the informed consent.

2. Dose escalation and expansion:

   1. Solid tumors: have a histologically confirmed relapsed or refractory advanced solid tumor for which no standard approved treatment is available, or is ineligible for, or did not tolerate standard approved treatment.
   2. NHL: have a histologically confirmed relapsed or refractory diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) or Mantle cell lymphoma (MCL) for which no standard approved treatment is available, or is ineligible for, or did not tolerate standard approved treatment.

3. Measurable/evaluable disease or documented relapse, respectively, relevant for tumor type as follows:

   1. Solid tumors: per Response evaluation criteria in solid tumors (RECIST) 1.1 with at least one target lesion
   2. NHL: Measurable disease defined as ≥1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on computed tomography (CT) scan or magnetic resonance imaging (MRI)

4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

5. All previous anti-cancer therapy-related AEs should have resolved to grade 1 or baseline value with the exception of alopecia and stable, treated endocrine toxicities of immune checkpoint inhibitors (ICIs) Note: Subjects with irreversible toxicity that in the opinion of the treating physician is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, hormone deficiency requiring replacement therapy) -

Exclusion Criteria

1. Known hypersensitivity to JBZ-001 or any of its excipients

2. Corrected interval between Q and T wave on ECG (QTc) ≥ 470 msec using Fredericia's formula.

3. Has significant and symptomatic cardiovascular disease (such as congestive heart failure New York Heart Association class III or higher, myocardial infarction, cerebrovascular disease, unstable angina, unstable arrhythmia) within the 3 months prior to first dose of JBZ-001.

4. Has another malignant disease requiring treatment, with the exception of curatively treated malignancies or malignancies with very low potential for recurrence or progression.

5. For solid tumor subjects:

   1. Symptomatic ascites or pleural effusion. A subject who is clinically stable for 2 weeks following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
   2. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks prior to study entry, as long as the dose is ≤ 4 mg of dexamethasone or equivalent per day

6. Known active HIV infection on antiretroviral therapy. Note: Testing is not required for eligibility.

7. Known active infection with hepatitis B or hepatitis C. Note: Testing is not required for eligibility.

8. Any other active infection requiring systemic therapy.

9. Major surgery (excluding procedures to stabilize the vertebrae) within 4 weeks or minor surgery within 2 weeks prior to first dose of JBZ-001.

10. Has a history of GI surgery or other procedures that might interfere with the absorption or swallowing of the study drug.

11. History or clinical evidence of any medical condition which the investigator judges as likely to interfere with the results of the study, poses an additional risk in participating, or makes the subject unlikely to comply with the study-related visits and assessments.

12. Female participants: pregnant or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental Cohort 3	JBZ-001	1\~6 subjects in this cohort will receive 1 dose of 10 mg orally daily
Experimental Cohort 2	JBZ-001	1\~6 subjects in this cohort will receive 1 dose 5 mg orally daily
Experimental Cohort 1	JBZ-001	1\~6 subjects in this cohort will receive 1 dose 5 mg orally.
Experimental Cohort 4	JBZ-001	1\~6 subjects in this cohort will receive 1 dose of 17.5 mg orally daily
Experimental Cohort 5	JBZ-001	1\~6 subjects in this cohort will receive 1 dose of 25 mg orally daily

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD）	28 days	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.
Phase II dose (RP2D)	28 days	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
Occurrence of all adverse events	28 Days	Evaluation of adverse events

Secondary Outcome Measures

Name	Time	Method
Maximum plasma concentration (Cmax）	28 days	Pharmacokinetic (PK) parameters after a single oral dose \& multiple doses
Time to Cmax (tmax)	28 days	Pharmacokinetic (PK) parameters after a single oral dose \& multiple doses
Area under the serum concentration-time curve (AUC[0-t]	28 days	Pharmacokinetic (PK) parameters after a single oral dose \& multiple doses
Area under the serum concentration-infinity curve AUC[0-infinity]	28 days	Pharmacokinetic (PK) parameters after a single oral dose \& multiple doses
Apparent terminal phase half-life (t1/2)	28 days	Pharmacokinetic (PK) parameters after a single oral dose
Overall Response Rate (ORR)	up to 1 year(anticipated)	The proportion of patients with complete response (CR) and partial response (PR)
Duration of response (DoR)	up to 1 year(anticipated)	The time from the date when the measurement criteria were met for complete or partial response (whichever occurred first) until the date of the first observed Progression Disease or death as a result of any cause.
Time to Progression (TTP)	up to 1 year(anticipated)	The time from clinical remission to disease progression.
Progression-free survival (PFS)	up to 1 year(anticipated)	The time the patient is enrolled to the date of any recorded disease progression or the death of any cause.

Trial Locations

Locations (1)

The Ohio State University; 🇺🇸 Columbus, Ohio, United States