A First-in-Human, Phase 1 Study of JAB-8263 in Adult Patients With Advanced Solid Tumors

Overview

This is a Phase 1, first-in-human, open-label study of JAB-8263 to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D) and assess the DLT. 30 subjects with advanced solid tumor will be enrolled.

Full Title of Study: “A Phase 1, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-8263 in Adult Subjects With Advanced Solid Tumors”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 30, 2022

Detailed Description

JAB-8263 is a small-molecule inhibitor of the highly conserved bromodomain pockets of the bromodomain and extraterminal (BET) proteins.

The objectives of this study are:

To determine the maximum-tolerated dose (MTD) and assess the dose-limiting toxicity (DLT) of JAB-8263 as a single agent to adult subjects with advanced solid tumors To assess the safety and tolerability of JAB-8263 To characterize the pharmacokinetic (PK) parameters and pharmacodynamics (PDc) To evaluate preliminary antitumor activity of JAB-8263

Interventions

  • Drug: JAB-8263
    • Variable dose, orally Q2D with 28 days each cycle

Arms, Groups and Cohorts

  • Experimental: JAB-8263
    • Monotherapy, dose escalation

Clinical Trial Outcome Measures

Primary Measures

  • Number of participants with dose limiting toxicities
    • Time Frame: Approximately 2.5 years
    • Incidence of dose limiting toxicities (DLTs) in the dose escalation phase. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first treatment cycle with JAB-8263
  • Find Recommended Phase 2 Dose (RP2D) of JAB-8263
    • Time Frame: Approximately 2.5 years
    • Measurements of MTD (i.e. the highest dose of JAB-8263 associated with the occurrence of Dose Limiting Toxicities (DLTs) in <33% of patients) or the RP2D (i.e. the highest tested dose that is declared safe and tolerable by the Investigators and Sponsor)

Secondary Measures

  • Number of participants with adverse events
    • Time Frame: Approximately 2.5 years
    • All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs, electrocardiograms, cardiac imaging and ophthalmological assessments
  • Area under the curve
    • Time Frame: Approximately 2.5 years
    • Area under the plasma concentration time curve of JAB-8263
  • Cmax
    • Time Frame: Approximately 2.5 years
    • Highest observed plasma concentration of JAB-8263
  • Tmax
    • Time Frame: Approximately 2.5 years
    • Time of highest observed plasma concentration of JAB-8263
  • T1/2
    • Time Frame: Approximately 2.5 years
    • Half life of JAB-8263
  • Objective response rate ( ORR )
    • Time Frame: Approximately 2.5 years
    • ORR is defined as the proportion of participants with complete response or partial response (CR+PR)
  • Duration of response ( DOR )
    • Time Frame: Approximately 2.5 years
    • DOR is defined as the time from the participant’s initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first.

Participating in This Clinical Trial

Inclusion Criteria

Subjects must meet all the following criteria in order to be included in the research study:

1. Subject must be ≥18 years-of-age at the time of signature of the informed consent form (ICF).

2. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

3. Subjects with histologically or cytologically confirmed advanced solid tumors which have progressed despite standard therapy(ies), or are intolerant to standard therapy(ies), or have a tumor for which no standard therapy(ies) exists.

4. Subjects with life expectancy ≥3 months.

5. Patients must have at least one measurable lesion as defined by RECIST v1.1.

6. Patients who have sufficient baseline organ function.

Exclusion Criteria

1. History (≤3 years) of cancer that is histologically distinct from the cancer under study.

2. Known serious allergy to investigational drug or excipients

3. Active brain or spinal metastases

4. History of pericarditis or Grade ≥2 pericardial effusion

5. History of interstitial lung disease.

6. History of Grade ≥2 active infections within 2 weeks

7. Known human immunodeficiency virus (HIV) infection

8. Seropositive for hepatitis B virus (HBV)

9. Seropositive for hepatitis C virus (HCV), or HCV-RNA viral levels are not detectable.

10. Any severe and/or uncontrolled medical conditions

11. History of myocardial infarction, unstable angina pectoris, coronary artery bypass graft, or cerebrovascular accident

12. Impaired cardiac function or clinically significant cardiac diseases

13. QTcF >470 msec at screening

14. History of medically significant thromboembolic events or bleeding diathesis

15. Unresolved Grade >1 toxicity

16. History of malignant biliary obstruction

17. Pregnant or breast-feeding

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Jacobio Pharmaceuticals Co., Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Jacobio Pharmaceuticals, Study Director, Jacobio Pharmaceuticals
  • Overall Contact(s)
    • Jacobio Pharmaceuticals, 86 10 56315466, clinicaltrials@jacobiopharma.com

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