Solid Tumors, Adult
Conditions
Keywords
BET inhibitor, Bromodomain and Extra-terminal
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.
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
DRUGJAB-8263
Variable dose, orally Q2D with 28 days each cycle
Sponsors
Jacobio Pharmaceuticals Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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. |
| T1/2 | Approximately 2.5 years | Half life of JAB-8263 |
| Area under the curve | Approximately 2.5 years | Area under the plasma concentration time curve of JAB-8263 |
Countries
United States
Outcome results
None listed