A Trial of the Combination of SHR-A1811 and Fluzoparib in HER2-Expressing Cancers

Study Overview
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Brief Summary
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The study is being conducted to evaluate safety, tolerability and preliminary efficacy of SHR-A1811 for Injection in combination with Fluzoparib Capsule for HER2-expressing advanced solid tumors of patients. To explore the reasonable dosage of dosage regimen of combination therapy for HER2-expressing advanced malignant tumors of patients.

Official Title
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A Phase Ⅰb/Ⅱ Clinical Study on the Dosage Exploration and Efficiency Expansion of SHR-A1811 for Injection in Combination With Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: SHR-A1811
* Drug: Fluzoparib Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged ≥18 years at the time of signing the ICF. At least one measurable lesion that meets RECIST 1.1 criteria in case of solid tumors. An Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1. Life expectancy ≥12 weeks. Adequate organ functions as defined. Swallow the drug pills normally. Exclusion Criteria: patients with active meningeal metastasis, or brain metastasis without surgical treatment or radiotherapy. Cancerous ascites and pleural effusion with clinical symptoms, which need puncture and drainage. Prior malignancy (other than current malignant tumor) within 5 years before the first dose of study treatment. History of autoimmune diseases. Not well controllable and serve cardiovascular disease. Prior lung disease with clinical significance. Occurrence of ≥ grade 2 of bleeding event within 4 weeks before the first dose, or currently receiving the anticoagulation. Active Hepatitis B and Hepatitis C; or serve infection with medication control. The grade of toxicity from the prior anti-cancer therapy not decrease to ≤ 1. Occurrence of intestinal obstruction and gastrointestinal perforation within 3 months before the first dose.

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
Intervention Model: Single Group Assignment
Interventional Model Description: SHR-A1811 for Injection in combination with Fluzoparib Capsule.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>SHR-A1811, Fluzoparib | Drug: SHR-A1811<br>* SHR-A1811 for Injection: Given IV.<br>Drug: Fluzoparib Capsule<br>* Fluzoparib Capsule: Given PO.<br>* Other names: SHR-3162;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limited Toxicity | Dose Limited Toxicity of SHR-A1811 for Injection in combination with Fluzoparib Capsule in Dose Exploration Period | first dose of study medication up to 21 days | 
| Recommended phase II dose | The Recommended phase II dose of SHR-A1811 for Injection in combination with Fluzoparib Capsule in Dose Exploration Period | first dose of study medication up to 21 days | 
| ORR | Objective Response Rate, Efficacy endpoints of SHR-A1811 for Injection in combination with Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients in indication expansion period | from the date of the first dose to the date of disease progression evaluated based on RECIST v1.1 criteria, or initiation of other anti-tumor treatment, whichever occurs first, up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DoR | Duration of response, Efficacy endpoints of SHR-A1811 for Injection in combination with Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients | from the date of the firstly documented tumor response (evaluated based on RECIST v1.1 criteria) to the date of the firstly documented disease progression (evaluated based on RECIST v1.1 criteria) or the date of death for any reason, up to 6 months | 
| DCR | Disease control rate, Efficacy endpoints of SHR-A1811 for Injection in combination with Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients | from the date of the first dose to the date of the firstly documented disease progression (evaluated based on RECIST v1.1 criteria) or the date of death for any reason, up to 6 months | 
| TTR | Time to Recovery, Efficacy endpoints of SHR-A1811 for Injection in combination with Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients | from the date of the first dose to the date of treatment termination, up to 6 months | 
| PFS | Progression-free survival, Efficacy endpoints of SHR-A1811 for Injection in combination with Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients | from the date of the first dose to the date of the firstly documented disease progression (evaluated based on RECIST v1.1 criteria) or the date of death for any reason, up to 6 months | 
| OS | Overall survival, Efficacy endpoints of SHR-A1811 for Injection in combination with Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients | from the date of the first dose to the date of death for any reason, up to 100 months | 
| 12 months' survival rate | Efficacy endpoints of SHR-A1811 for Injection in combination with Fluzoparib Capsule in HER2-Expressing Advanced Solid Tumors of Patients | from the date of the first dose up to 12 months | 
| Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) | Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | from signature completion of ICF to 30 days after the last dose or to the beginning of the new anti-cancer therapy, up to 6 months | 
| The occurrence rate of dose titration due to AE related with study medication | The occurrence rate of dose interruption, dose decrease and dose termination because of study drug related toxicity during the study | from signature completion of ICF to 30 days after the last dose or to the beginning of the new anti-cancer therapy, up to 6 months | 
| Cmin | PK concentration of Fluzoparib Capsule | 10 min before first dose of Fluzoparib Capsule in C1D8 to 10 min before first dose of Fluzoparib Capsule in C8D1 | 
| C3h | PK concentration of Fluzoparib Capsule | 3 hour after first dose of Fluzoparib Capsule in C2D1 | 
| AUC0-t | PK parameters of SHR-A1811 for Injection | the date of first dose to 30 days after last dose | 
| Cmin | PK parameters of SHR-A1811 for Injection | the date of first dose to 30 days after last dose | 
| Cmax | PK parameters of SHR-A1811 for Injection | the date of first dose to 30 days after last dose | 
| ADA | Anti-drug antibody, Immunogenicity of SHR-A1811 for Injection | the date of first dose up to 90 days after last dose | 
| NAb | Neutralizing Antibody, Immunogenicity of SHR-A1811 for Injection | the date of first dose up to 90 days after last dose |