A Phase I Clinical Study of SHR-A2009 for Injection in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study is an open-label, multicenter Phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics and efficacy of SHR-A2009 for injection in patients with advanced solid tumors.

Official Title
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A Phase I, Open-Label, Multicenter Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of SHR-A2009 for Injection in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: SHR-A2009


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumors which is relapsed or refractory to standard treatment, or lack of standard treatment, or standard treatment is not applicable currently; Have at least one measurable tumor lesion per RECIST v1.1 (patients with only non-target lesions are allowed to be enrolled in dose escalation stage); ECOG performance status of 0-1; Life expectancy ≥ 12 weeks; Adequate bone marrow and organ function . Subjects must voluntarily agree to participate in the trial and sign a written informed consent form. Exclusion Criteria: Patients with symptomatic central nervous system metastases or meningeal metastases; Ongoing or previous anti-tumor therapies within 4 weeks prior to the first dose of study drug; Prior treatment with antibody-drug conjugate (ADC) consisting of topoisomerase I inhibitors; History of serious cardiovascular and cerebrovascular diseases; Severe infection within 4 weeks prior to the first dose; Adverse reactions of previous anti-tumor treatment have not recovered to Grade ≤ 1 per NCI-CTCAE v5.0.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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-A2009
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-A2009 for Injection will be administrated per dose level in which the patients are assigned.<br> | Drug: SHR-A2009<br>* In dose Escalation: SHR-A2009 will be administered intravenously. Six dose levels are preset. In dose Expansion: 2 to 3 dose cohorts will be selected for dose expansion stage. In indication Expansion: Indications will be selected to evaluate preliminary efficacy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) or maximum administered dose (MAD). | Incidence and category of dose limiting toxicities (DLTs) during the first 21-day cycle of SHR-A2009 treatment. | From Day 1 to Day 21 | 
| Recommended Phase 2 dose (RP2D) | RP2D will be determined on the basis of evaluation on MTD/MAD, PK, efficacy data in dose escalation and dose expansion stages. | From Day 1 to 90 days after last dose | 
| Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) ([CTCAE] v5.0) | Assess safety and tolerability of SHR-A2009 by way of adverse events (CTCAE v5.0). | From Day 1 to 90 days after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax of SHR-A2009 | Time to maximum concentration of SHR-A2009 | approximately 6 months | 
| Cmax of SHR-A2009 | Maximum concentration of SHR-A2009 | approximately 6 months | 
| AUC0-t of SHR-A2009 | area under the concentration-time curve from time 0 to the last measurable concentration time point of SHR-A2009 | approximately 6 months | 
| AUC0-∞ of SHR-A2009 | area under the concentration-time curve from time 0 to infinity of SHR-A2009 | approximately 6 months | 
| Immunogenicity of SHR-A2009 | Anti-SHR-A2009 antibody (ADA) | approximately 9 months | 
| Overall response rate (ORR) | Evaluated using RECIST 1.1 | approximately within 36 months | 
| Duration of response (DoR) | Evaluated using RECIST 1.1 | approximately within 36 months | 
| Disease control rate (DCR) | Evaluated using RECIST 1.1 | approximately within 36 months | 
| Progression-free survival (PFS) | Evaluated using RECIST 1.1 | approximately within 36 months |