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

Study Overview
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Brief Summary
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This is a Phase 1/2a, open-label, multi-center study of JAB-3068 in Patients with advanced solid tumors.This study has two phases: dose escalation phase and dose expansion phase.

Detailed Description
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Dose escalation study phase is designed to determine the maximum tolerated dose (MTD) according to a 3+3 design and recommended phase II dose (RP2D) and to characterize the safety, tolerability, and pharmacokinetics (PK) profile of JAB-3068. Other dose regimens may be explored based on the analysis of emerging PK and safety data. at this study phase, JAB-3068 dministered orally once daily (QD) or twice daily (BID) or once every other day (QOD) in 28-day treatment cycles to adult patients with advanced solid tumors, Dose expansion study phase is designed to evaluate the antitumor activity(ORR and DOR) of JAB-3068 in patients with NSCLC, ESCC and HNSCC.

Official Title
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A Phase 1/2a, Multi-Center, Dose Escalation/Dose Expansion, 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
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Non-small Cell Lung Cancer, Head and Neck Cancer, Esophageal Cancer, Other Metastatic Solid Tumors

Intervention / Treatment
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* Drug: JAB-3068


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained prior to any study-related procedure being performed; Age 18 years or older; Dose escalation(phase I): Patients with histologically or cytologically confirmed, advanced solid tumors (including lymphoma) which have progressed from standard therapy or for whom no standard therapy exists; Dose expansion(phase IIa ): Patients with histologically or cytologically confirmed, advanced NSCLC, ESCC, HNSCC which have progressed from standard therapy; Patients with life expectancy ≥3 months; Dose expansion(phase IIa ): patients have available archival tissue can be provided or willing to perform biopsy to provide fresh tumor tissue. Patients with other solid tumors must have at least one measurable lesion as defined by RECIST v1.1;Patients with Lymphomas must have at least one measurable lesion as defined by IWG 2007 criteria; 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; Lymphoma with brain metastasis; Other solid tumors: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 prior to the first dose of JAB-3068. Use of an investigational drug during the past 30 days prior to the first dose of JAB-3068.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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>JAB-3068 will be administered orally in the morning following a fast of approximately 6 hours before on PK collection. Patients will continue to fast for approximately 2 hours after the administration of JAB-3068. On non-PK days patients will fast approximately 2 hours before JAB-3068 and continue to fast for approximately 2 hours afterwards. | Drug: JAB-3068<br>* 25 mg,100 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose limiting toxicities | Number of participants with 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. | At the end of Cycle 1 (each cycle is 28 days) | 
| Objective response rate | ORR is defined as the proportion of participants with complete response or partial. the ORR of JAB-3068 in patients with ESCC, NSCLC and HNSCC will be evaluated separately in dose expansion | 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. The DOR of JAB-3068 in patients with ESCC, NSCLC and HNSCC will be evaluated separately in dose expansion | Approximately 2 years | 

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) in dose escalation. | 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 in dose escalation. | Approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JAB-3068, SHP2, PTPN11, ESCC, NSCLC, HNSCC, Colorectal cancer (CRC), EGFR