Clinical trial NCT04686682: A First-in-Human, JAB-8263 in Adult Patients With Advanced Tumors
Official title: A Phase I/IIa, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-8263 in Adult Patients With Advanced Malignant Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: NSCLC
SCLC
CRPC
ESCC
Ovarian Carcinoma
AML
MF
Malignant Tumor
Lead sponsor: Jacobio Pharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-12-29
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1/2a, first-in-human, open-label study of JAB-8263, this study has two parts: solid tumor dose escalation and expansion study and hematology tumor dose escalation and expansion study.

These two parts will determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D) and assess the DLT of JAB-8263 in treatment with patients with advanced solid tumors and hematology tumors separately. 30 subjects each will be enrolled.

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 malignant 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

Eligibility criteria: 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 recurrent/refractory AML according to WHO 2016
  5. Subjects with life expectancy ≥3 months.
  6. Patients with solid tumor must have at least one measurable lesion as defined by RECIST v1.1.
  7. 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

Primary outcomes:
measure: Number of participants with dose limiting toxicities
timeFrame: Approximately 18 months
Secondary outcomes:
measure: Number of participants with adverse events
timeFrame: Approximately 18 months
measure: Area under the curve
timeFrame: Approximately 18 months
measure: Cmax
timeFrame: Approximately 18 months
measure: Tmax
timeFrame: Approximately 18 months
measure: T1/2
timeFrame: Approximately 18 months
measure: Objective response rate ( ORR )
timeFrame: Approximately 18 months
measure: Duration of response ( DOR )
timeFrame: Approximately 18 months
measure: Duration of response ( DCR )
timeFrame: Approximately 18 months
measure: CR without minimal residual disease rate (CR MRD-)
timeFrame: Approximately 18 months
measure: Overall response rate
timeFrame: Approximately 18 months
measure: Event-free survival( EFS)
timeFrame: Approximately 18 months
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin
state: Tianjin
Study officials:
affiliation: Jacobio Pharmaceuticals
name: Jacobio Pharmaceuticals
role: STUDY_DIRECTOR
References: