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

Study Overview
=================
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.

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

Conditions
-----------------
Non-small Cell Lung Cancer, Head and Neck Cancer, Esophageal Cancer, Other Metastatic Solid Tumors

Intervention / Treatment
-----------------
* Drug: JAB-3068


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JAB-3068 (SHP2 inhibitor)<br>Daily oral administration of JAB-3068 | Drug: JAB-3068<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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-3068. | up to 28-day per cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 years | 
| Area under the curve | Area under the plasma concentration time curve of JAB-3068 | Approximately 2 years | 
| Cmax | Highest observed plasma concentration of JAB-3068 | Approximately 2 years | 
| Tmax | Time of highest observed plasma concentration of JAB-3068 | Approximately 2 years | 
| T1/2 | Half life of JAB-3068 | Approximately 2 years | 
| Objective response rate | ORR is defined as the proportion of participants with complete response or partial response (CR+PR) | Approximately 2 years | 
| Duration of response | 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 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
JAB-3068, SHP2, advanced solid tumor, NSCLC, ESCC, HNSCC, PTPN11, EGFR, Colorectal cancer