A First in Human, Dose Escalation Study of JAB-3068 （SHP2 Inhibitor） in Adult Patients With Advanced Solid Tumors

Sponsor

Jacobio Pharmaceuticals Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03518554

Collaborator

(none)

Enrollment

Locations

Arm

38.3

Anticipated Duration (Months)

11.3

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 1, multi-center, dose escalation, open-label study to evaluate the safety, tolerability, pharmacokinetics, and preliminary evidence of antitumor activity of JAB-3068 in adult patients with advanced solid.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer Head and Neck Cancer Esophageal Cancer Other Metastatic Solid Tumors	Drug: JAB-3068	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1, Multi-Center, Dose Escalation, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-3068 in Adult Patients With Advanced Solid Tumors

Actual Study Start Date :

Apr 23, 2018

Anticipated Primary Completion Date :

Jul 1, 2021

Anticipated Study Completion Date :

Jul 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: JAB-3068 (SHP2 inhibitor) Daily oral administration of JAB-3068	Drug: JAB-3068 JAB-3068 will be orally administered on a daily basis. Patients need to fast 2 hours before （6 hours for PK days) and 2 hours after each dosing.

Arm

Intervention/Treatment

Experimental: JAB-3068 (SHP2 inhibitor)

Daily oral administration of JAB-3068

Drug: JAB-3068

JAB-3068 will be orally administered on a daily basis. Patients need to fast 2 hours before （6 hours for PK days) and 2 hours after each dosing.

Outcome Measures

Primary Outcome Measures

Number of participants with dose limiting toxicities [up to 28-day per cycle]
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-3068.

Secondary Outcome Measures

Number of participants with adverse events [Approximately 2 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 years]
Area under the plasma concentration time curve of JAB-3068
Cmax [Approximately 2 years]
Highest observed plasma concentration of JAB-3068
Tmax [Approximately 2 years]
Time of highest observed plasma concentration of JAB-3068
T1/2 [Approximately 2 years]
Half life of JAB-3068
Objective response rate [Approximately 2 years]
ORR is defined as the proportion of participants with complete response or partial response (CR+PR)
Duration of response [Approximately 2 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.

Other Outcome Measures

pERK [Approximately 2 years]
On treatment versus baseline comparison of pharmacodynamic marker pERK (Phosphorylated form of Extracellular signal-regulated kinase) on newly obtained tumor biopsy samples by IHC.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Written informed consent obtained prior to any study-related procedure being performed;
Age 18 years or older;
Patients with histologically or cytologically confirmed, advanced solid tumors which have progressed despite standard therapy or for whom no standard therapy exists;
Patients with life expectancy ≥3 months;
Patients must have at least one measurable lesion as defined by RECIST v1.1;
Eastern Cooperative Oncology Group performance score 0 or 1;
Patients who have sufficient baseline organ function.

Exclusion Criteria:

Patients with life-threatening autoimmune disease or with autoimmune disorder and who are on long-term steroid treatment;
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO;
Known malignant central nervous system (CNS) disease other than neurologically stable, treated brain metastases;
Active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV)
Patients who have any severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the Investigator and Sponsor, could affect the patient's participation in the study
Patients who have impaired cardiac function or clinically significant cardiac diseases;
Use of anti-cancer treatment drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of JAB-3068;
Use of an investigational drug during the past 30 days or 5 half-lives (whichever is shorter) prior to the first dose of JAB-3068;
No other anti-cancer therapy (chemotherapy, immunotherapy, hormonal therapy radiotherapy (except for palliative local radiotherapy), biological therapy or other novel agent is to be permitted while the patient is receiving study medication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HealthONE Clinic Services Oncology-Hematology	Denver	Colorado	United States	80202
2	Florida Cancer Specialists	Sarasota	Florida	United States	37203
3	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
4	The University of Texas M. D. Anderson Cancer Center	Houston	Texas	United States	77030