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

Solid Tumors, Adult Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04587479
• Other study ID #: JAB-8263-1001
• Status: Recruiting
• Phase: Phase 1
• Start date: November 23, 2020
• Est. completion date: April 30, 2023

Study information

• Verified date: March 2022
• Source: Jacobio Pharmaceuticals Co., Ltd.
• Contact: Jacobio Pharmaceuticals
• Phone: 86 10 56315466
• Email: clinicaltrials[@]jacobiopharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 30, 2023
• Est. primary completion date: April 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors, Adult

Intervention

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

Locations

Country	Name	City	State
United States	SCRI HeatlthONE	Denver	Colorado
United States	Florida Cancer Center, Lake Mary	Lake City	Florida
United States	Tennessee Oncology Nashville	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Jacobio Pharmaceuticals Co., Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with dose limiting toxicities	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	Approximately 2.5 years
Primary	Find Recommended Phase 2 Dose (RP2D) of JAB-8263	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)	Approximately 2.5 years
Secondary	Number of participants with adverse events	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	Approximately 2.5 years
Secondary	Area under the curve	Area under the plasma concentration time curve of JAB-8263	Approximately 2.5 years
Secondary	Cmax	Highest observed plasma concentration of JAB-8263	Approximately 2.5 years
Secondary	Tmax	Time of highest observed plasma concentration of JAB-8263	Approximately 2.5 years
Secondary	T1/2	Half life of JAB-8263	Approximately 2.5 years
Secondary	Objective response rate ( ORR )	ORR is defined as the proportion of participants with complete response or partial response (CR+PR)	Approximately 2.5 years
Secondary	Duration of response ( DOR )	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.	Approximately 2.5 years