A Study of SHR-4602 in Subjects With Advanced Malignant Solid Tumors

Study Overview
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Brief Summary
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This is an open-label, three-part study to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of SHR-4602 and preliminary anti-tumor efficacy in HER2 expressing or mutated advanced malignant solid tumor subjects.

Official Title
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A Phase I Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of SHR-4602 in HER2 Expressing or Mutated Advanced Malignant Solid Tumor Subjects

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: SHR-4602 for injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced/unresectable or metastatic solid tumor with HER2 expression or mutation that is refractory to or intolerable with standard treatment, or for which no standard treatment is available; At least one measurable lesion based on RECIST v1.1 criteria; ECOG PS score: 0-1 points; Expected survival period ≥ 3 months; Adequate organ function; Must take one medically approved contraceptive measure; Patients voluntarily joined the study and signed informed consent. Exclusion Criteria: Patients with known CNS metastasis or hepatic encephalopathy; Suffering from peripheral neuropathy; History of clinically significant lung diseases (e.g., interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or suspected to have these diseases by imaging at screening period; Patients with any active, known or suspected autoimmune disorder; With known severe allergic reactions to any other monoclonal antibodies; Patients with symptomatic ascites or pleural effusion requiring paracentesis and drainage, or patients who have undergone ascites or pleural effusion drainage within 2 weeks before the first dose; Patients with other malignancies currently or within the past 5 years; Uncontrolled cardiac diseases or symptoms; With known hereditary or acquired bleeding (e.g., coagulopathy) or a tendency to clot (e.g., hemophiliacs); Patients with other potential factors that may affect the study results.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open-label, three-part study to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of SHR-4602 and preliminary anti-tumor efficacy in HER2 expressing or mutated advanced malignant solid tumor subjects. Include three stages: dose escalation, PK expansion, and efficacy expansion.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose escalation<br> | Drug: SHR-4602 for injection<br>* be administered via intravenous (IV) infusion<br>|
| Experimental: Part 2: PK expansion<br> | Drug: SHR-4602 for injection<br>* be administered via intravenous (IV) infusion<br>|
| Experimental: Part 3: efficacy expansion<br> | Drug: SHR-4602 for injection<br>* be administered via intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (AEs) |  | From Day 1 to 90 days after last dose | 
| Maximum tolerated dose (MTD) |  | From Day 1 to 21 days after first dose | 
| Dose Limiting Toxicities (DLT) |  | From Day 1 to 21 days after first dose | 
| Recommended Phase 2 dose (RP2D) |  | From Day 1 to 90 days after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters of SHR-4602 for Injection: Cmax |  | the date of first dose to 30 days after last dose | 
| PK parameters of SHR-4602 for Injection: AUC0-t |  | the date of first dose to 30 days after last dose | 
| PK parameters of SHR-4602 for Injection: Tmax |  | the date of first dose to 30 days after last dose | 
| PK parameters of SHR-4602 for Injection: T1/2 |  | the date of first dose to 30 days after last dose | 
| ADA | Anti-drug antibody, Immunogenicity of SHR-4602 for Injection | the date of first dose up to 90 days after last dose | 
| ORR | Objective Response Rate, Efficacy endpoints of SHR-4602 for Injection，As assessed by RECIST v1.1 | the date of first dose up to 90 days after last dose | 
| DCR | Disease control rate, Efficacy endpoints of SHR-4602 for Injection，As assessed by RECIST v1.1 | the date of first dose up to 90 days after last dose | 
| DOR | Duration of response, Efficacy endpoints of SHR-4602 for Injection，As assessed by RECIST v1.1 | the date of first dose up to 90 days after last dose | 
| PFS | Progression Free Survival, Efficacy endpoints of SHR-4602 for Injection，As assessed by RECIST v1.1 | the date of first dose up to 90 days after last dose |