A Study to Investigate Safety and Tolerability of SH3809 Tablet in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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The primary objective is to determine the safety and tolerability of SH3809 in subjects with advanced solid tumors. The second objective is to evaluate the PK profile and preliminary efficacy of SH3809 in solid tumors.

Detailed Description
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This is a phase I, open-label study to assess the safety,tolerability, pharmacokinetics and preliminary efficacy of SH3809 tablet, a small molecule inhibitor of SHP2 receptor , in patients with advanced solid tumors.

Official Title
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A Phase I, Open-Label Study to Determine Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Efficacy of SH3809 Tablet in Patients With Advanced Solid Tumors in China

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: SH3809 tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 75 years inclusive; Histologically or cytologically confirmed advanced malignant solid tumors, eligible patients should be either refractory or intolerant to all available therapies known to confer a clinical benefit as determined by the investigator, except for primary hepatic carcinoma; Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1; Life expectancy ≥ 3 months; Adequate hematologic, hepatic and renal function; Participant willing to agree to not father a child/become pregnant and comply with effective contraception criteria; Provision of signed and dated, written informed consent prior to any study-specific evaluation. Exclusion Criteria: Previous treatment with any SHP2 inhibitors; Spinal cord compression, meningeal metastases or brain metastases unless asymptomatic, stable and not requiring steroids for at least 2 weeks prior to start of study treatment; Life-threatening autoimmune disease or autoimmune disorder with long-term steroid treatment; Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and treponema pallidum (TP); Patients who have impaired cardiac function or clinically significant cardiac diseases; Active, clinically significant interstitial lung disease or pneumonitis; Females who are pregnant or breastfeeding; Judgment by the investigator that the patient should not participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Daily oral administration of SH3809 tablet<br> | Drug: SH3809 tablet<br>* Starting dose 2mg,oral administered once daily. If tolerated subsequent cohorts will test increasing doses (4mg,6mg,8mg,10mg,12mg) of SH3809.<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 (DLTs) | Incidence and nature of DLTs in the dose escalation phase | Within the first 28 days of consecutive treatment | 
| Maximum tolerated dose(MTD) |  | Within the first 28 days of consecutive treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Highest observed plasma concentration of SH3809 | 4 weeks | 
| Tmax | Time of highest observed plasma concentration of SH3809 | 4 weeks] | 
| T1/2 | Elimination half-life of SH3809 | 4 weeks | 
| Area Under the Curve (AUC) | Area under the plasma concentration time curve of SH3809 | 4 weeks | 
| Overall Response Rate(ORR) | Overall response rate of SH3809 per RECIST v1.1 | up to 12 months | 
| Progression-free survival(PFS) |  | up to 12 months | 
| Disease control rates(DCR) | Disease control rates of SH3809 per RECIST v1.1 | up to 12 months | 
| Duration of response(DOR) | Duration of response of SH3809 per RECIST v1.1 | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced solid tum, SHP2, EGFR, NSCLC, Colorectal cancer, KRAS G12