A Study of JAB-3312 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, open-label dose-escalation study to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and assess the DLT of JAB-3312. It is anticipated that approximately 24 subjects will be enrolled in the dose-escalation phase of the study. JAB-3312 will be administered orally once daily (QD) in 21-day treatment cycles.

Official Title
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A Phase 1, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-3312 in Adult Patients With Advanced Solid Tumors

Conditions
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Non-small Cell Lung Cancer, Colorectal Cancer, Pancreatic Ductal Carcinoma, Esophageal Squamous Cell Carcinoma, Head and Neck Squamous Cell Carcinoma, Breast Cancer, Other Solid Tumors

Intervention / Treatment
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* Drug: JAB-3312


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be ≥18 years-of-age at the time of signature of the informed consent form (ICF). Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. Subjects with histologically or cytologically confirmed advanced solid tumors which have progressed despite standard therapy or for which no standard therapy exists. Subjects with life expectancy ≥3 months. Patients must have at least one measurable lesion as defined by RECIST v1.1. Patients who have sufficient baseline organ function Exclusion Criteria: Severe autoimmune disease (including immune-related adverse events of prior immune-oncology therapy) or autoimmune disorder that requires chronic systemic corticosteroid treatment at immunosuppressive doses (prednisone >10 mg/day or equivalent). Known malignant central nervous system disease other than neurologically stable, treated brain metastases. History or evidence of interstitial lung disease, radiation pneumonitis which required steroid treatment, or idiopathic pulmonary fibrosis, pleural or pericardial effusion that required intervention such as a drain. History of seropositive status for hepatitis B, hepatitis C and human immunodeficiency virus (HIV). History or evidence of active infections (Grade ≥2). History or evidence of significant inflammatory or vascular eye disorder. History of an allogeneic bone marrow or solid organ transplant. Use of systemic anti-cancer agent (except for anti-androgen therapy for prostate cancer) or investigational drug ≤28 days prior to the first dose of JAB-3312. History of radiation therapy ≤28 days prior to the first dose of JAB-3312, or likely to require radiation therapy at any time until the 30 days after the last dose of JAB-3312. History of transfusion of whole blood, red blood cell or platelet packets ≤2 weeks before the start of treatment. Subjects experiencing unresolved Grade >1 toxicity before the start of treatment

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: Sequential Assignment
Interventional Model Description: Proposed dose Cohorts Cohort A：1mg Cohort B：2mg Cohort C：4mg Cohort D: 6mg Cohort E：8mg
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JAB-3312<br>JAB-3312 will be administered orally once daily in 21 days treatment cycles. | Drug: JAB-3312<br>* JAB-3312 will be supplied as 0.25 mg, 1.0 mg and 4.0 mg capsules.<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 | 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-3312. | Approximately 2 years | 
| Find Recommended Phase 2 Dose (RP2D) of JAB-3312 | Measurements of MTD (i.e. the highest dose of JAB-3312 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 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-3312 | Approximately 2 years | 
| Cmax | Highest observed plasma concentration of JAB-3312 | Approximately 2 years | 
| Tmax | Time of highest observed plasma concentration of JAB-3312 | Time of highest observed plasma concentration of JAB-3312 | 
| T1/2 | Half life of JAB-3312 | Approximately 2 years | 
| Objective response rate ( ORR ) | ORR is defined as the proportion of participants with complete response or partial response (CR+PR) | Approximately 2 years | 
| 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 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Src homology phosphatase 2 (SHP2), PTPN11, Kirsten rat sarcoma (KRAS) proto-oncogene, GTPase, epidermal growth factor receptor (EGFR)