A Study of SHR-A1811 in Subjects With Advanced Malignant Solid Tumors

Study Overview
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Brief Summary
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This is an open-label, two-part study to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of SHR-A1811 and preliminary anti-tumor efficacy in HER2 expressing or mutated advanced malignant solid tumor subjects.

Official Title
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A Phase 1 Multi-Country, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of SHR-A1811 in HER2 Expressing or Mutated Advanced Malignant Solid Tumor Subjects

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: SHR-A1811


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 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 LVEF ≥ 50% by either ECHO or MUGA Has adequate renal and hepatic function Female subjects agree not to be pregnant or lactating from beginning of the study screening until 6 months after receiving the last treatment Exclusion Criteria: 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 Known hereditary or acquired bleeding and thrombotic tendency

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Dose escalation<br> | Drug: SHR-A1811<br>* be administered via intravenous (IV) infusion<br>|
| Experimental: Part 2 Indication expansion<br> | Drug: SHR-A1811<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) | Frequency and seriousness of treatment emergent adverse events (TEAEs) | From Day1 to 90 days after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameter: Tmax of SHR-A1811 | Time to maximal concentration (Tmax) of SHR-A1811 | Through study completion, an average of 1 year | 
| PK parameter: Cmax of SHR-A1811 | Maximal concentration (Cmax) of SHR-A1811 | Through study completion, an average of 1 year | 
| PK parameter: AUC0-t of SHR-A1811 | AUC computed from time zero to the time of the last quantifiable concentration (AUC0-t) of SHR-A1811 | Through study completion, an average of 1 year | 
| Immunogenicity of SHR-A1811 | Including anti-drug antibody and/or neutralizing antibody | Through study completion, an average of 1 year | 
| Tumor response using RECIST 1.1 | RECIST=Response Evaluation Criteria in Solid Tumors Assessment of tumor response until disease progression or death to evaluate the efficacy of SHR-A1811 up to 30 months | From first dose to disease progression or death, whichever comes first, up to 30 months |