A First-in-Human Study of JAB-8263 in Adult Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: JAB-8263 Monotherapy, dose escalation |
Drug: JAB-8263
Variable dose, orally Q2D with 28 days each cycle
|
Outcome Measures
Primary Outcome Measures
- Number of participants with dose limiting toxicities [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 [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 Outcome Measures
- Number of participants with adverse events [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 [Approximately 2.5 years]
Area under the plasma concentration time curve of JAB-8263
- Cmax [Approximately 2.5 years]
Highest observed plasma concentration of JAB-8263
- Tmax [Approximately 2.5 years]
Time of highest observed plasma concentration of JAB-8263
- T1/2 [Approximately 2.5 years]
Half life of JAB-8263
- Objective response rate ( ORR ) [Approximately 2.5 years]
ORR is defined as the proportion of participants with complete response or partial response (CR+PR)
- Duration of response ( DOR ) [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
Subjects must meet all the following criteria in order to be included in the research study:
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Subject must be ≥18 years-of-age at the time of signature of the informed consent form (ICF).
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Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
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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.
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Subjects with life expectancy ≥3 months.
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Patients must have at least one measurable lesion as defined by RECIST v1.1.
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Patients who have sufficient baseline organ function.
Exclusion Criteria:
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History (≤3 years) of cancer that is histologically distinct from the cancer under study.
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Known serious allergy to investigational drug or excipients
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Active brain or spinal metastases
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History of pericarditis or Grade ≥2 pericardial effusion
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History of interstitial lung disease.
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History of Grade ≥2 active infections within 2 weeks
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Known human immunodeficiency virus (HIV) infection
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Seropositive for hepatitis B virus (HBV)
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Seropositive for hepatitis C virus (HCV), or HCV-RNA viral levels are not detectable.
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Any severe and/or uncontrolled medical conditions
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History of myocardial infarction, unstable angina pectoris, coronary artery bypass graft, or cerebrovascular accident
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Impaired cardiac function or clinically significant cardiac diseases
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QTcF >470 msec at screening
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History of medically significant thromboembolic events or bleeding diathesis
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Unresolved Grade >1 toxicity
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History of malignant biliary obstruction
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Pregnant or breast-feeding
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | SCRI HeatlthONE | Denver | Colorado | United States | 80218 |
| 2 | Florida Cancer Center, Lake Mary | Lake City | Florida | United States | 32025 |
| 3 | Tennessee Oncology Nashville | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- Jacobio Pharmaceuticals Co., Ltd.
Investigators
- Study Director: Jacobio Pharmaceuticals, Jacobio Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- JAB-8263-1001