A Study of SHR-A1811 in Subjects With Advanced Non-small Cell Lung Cancer

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 efficacy of SHR-A1811 for injection in subjects with advanced non-small cell lung cancer who have HER2 expression , amplification, or mutation

Official Title
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Phase I/II Clinical Study of the Safety, Tolerability, Pharmacokinetics, and Efficacy of SHR-A1811 for Injection in Subjects With Advanced Non-small Cell Lung Cancer Who Have HER2 Expression , Amplification, or Mutation

Conditions
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Advanced Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: SHR-A1811


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide a written informed consent Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 advanced non-small cell lung cancer with HER2 expression , amplification, or mutation has previously received platinum-based chemotherapy for advanced or metastatic NSCLC, has developed disease progression during or after treatment, or is unable to tolerate platinum-based chemotherapy. There is at least one measurable lesion according to RECIST V1.1 criteria Exclusion Criteria: Has unresolved toxicities from previous anticancer therapy, defined as toxicities not yet resolved to NCI-CTCAE version 5.0 grade ≤ 1. Has received HER2 antibody drug conjugates, Central nervous system metastasis or meningeal metastasis with clinical symptoms Has active infection requiring systemic treatment.

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
Interventional Model Description: Single arm study of SHR-A1811
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-A1811<br>SHR-A1811 was administered intravenously every 3 weeks (Q3W) until discontinuation treatment | Drug: SHR-A1811<br>* Phase 1 Drug: SHR-A1811 There are four pre-defined dose regimens . Subjects will be enrolled with an initial dose Phase 2 Drug: SHR-A1811 Doses will be determined from Phase 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1:Incidence of Adverse Events (AEs) by CTCAE v5.0 of SHR-A1811 | Assess safety and tolerability of SHR-A1811 by way of adverse events (CTCAE v5.0) | From Day 1 to90 days after last dose ，appropriately to 3 years | 
| Phase 1:Severity of Adverse Events (AEs) by CTCAE v5.0 of SHR-A1811 | Assess safety and tolerability of SHR-A1811 by way of adverse events (CTCAE v5.0) | From Day 1 to90 days after last dose ，appropriately to 3 years | 
| Phase1: Maximum tolerated dose (MTD) | Incidence rate and category of dose limiting toxicities (DLTs) during the first 21-day cycle of SHR-A1811 treatment | 12 months | 
| Phase 1: Recommended Phase 2 dose (RP2D) | RP2D was determined based on the safety, tolerability, PK, immunogenicity data and efficacy information obtained | 12 months | 
| Phase2:ObjectiveResponse Rate (ORR) | As assessed by RECIST v1.1 , as assessed by independent review committee (IRC) | Subjects were evaluated on tumor imaging every 6 weeks after treatment initiation and every 12 weeks after 54 weeks, until imaging progression, initiation of new antitumor therapy, loss of follow-up, and death，appropriately to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1：PK parameter ：Tmax of SHRA1811 | Time to maximal concentration (Tmax) of SHR-A1811 | appropriately to 3 years | 
| Phase1:PK parameter: Cmax of SHR-A1811 | Maximal concentration (Cmax) of SHR-A1811 | appropriately to 3 years | 
| Phase1: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 | appropriately to 3 years | 
| Phase1:Immunogenicity of SHR-A1811 | Including anti-drug antibody and/or neutralizing antibody | Immunogenicity sample collection time points include: within 30 min before administration of C1D1, C2D1, C3D1, C4D1, C6D1 and C8D1 starting from cycle 11 only in every 3 cycles ,appropriately to 3 years | 
| Phase2:Progression Free Survival (PFS) | As assessed by RECIST v1.1 , as assessed by independent review committee (IRC) and investigator | appropriately to 3 years | 
| Phase2:ObjectiveResponse Rate (ORR) | As assessed by RECIST v1.1 , as assessed by investigator | appropriately to 3 years | 
| Phase2:Duration of response (DOR) | As assessed by RECIST v1.1 , as assessed by independent review committee (IRC) and investigator | appropriately to 3 years | 
| Phase2:Disease control rate (DCR) | As assessed by RECIST v1.1 , as assessed by independent review committee (IRC) and investigator | appropriately to 3 years | 
| Phase2:Overall survival (OS) |  | Approximately 5 years after last subject enrolled |