A Trial of SHR-1210 (an Anti-PD-1 Inhibitor) in Combination With Apatinib and Fluzoparib in Patients With TNBC

Study Overview
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Brief Summary
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The study is being conducted to evaluate the tolerability, safety and efficacy of SHR-1210 in combination with Apatinib and Fluzoparib in subjects with recurrent and metastatic triple negative breast cancer

Detailed Description
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Drug: SHR-1210 + Apatinib +Fluzoparib SHR-1210 will be administered as an intravenous infusion, Apatinib tablets will be given orally, Fluzoparib capsule will be given orally 28 days per cycle, until disease progression or unacceptable toxicity. Treatment group ： PD-1 antibody SHR-1210 combination with apatinib and fluzoparib

Official Title
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A Phase Ib，Open-labeled, Multi-center, Dose-exploring Trial of SHR-1210 (Anti-PD-1 Antibody) in Combination With Apatinib and Fluzoparib in Subjects With Recurrent and Metastatic Triple Negative Breast Cancer

Conditions
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Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: SHR-1210 + Apatinib +Fluzoparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed the informed consent. Female aged ≥18 years old. Histologically diagnosed patients with recurrent and metastatic triple negative breast cancer. No more than 2-line chemotherapy failed at the stage of recurrence and metastasis . Patients who have been treated with platinum-based regimen at the stage of recurrence/metastasis need non-disease progression (non-pd)during treatment At least one measuring lesion that confirmed by RECIST v1.1 standard. The patients can swallow pills. Have a life expectancy of at least 12 weeks. The functions of vital organs meet protocal requirements. Exclusion Criteria: Subjects had any history of active autoimmune disease . Subjects had previously been treated with anti-PD-1 and PD-L1 antibodies, or was known to be allergic to antibody drugs, or had previously been treated with apatinib, or had previously been treated with PARP inhibitors. Subjects have untreated central nervous system metastasis. History of hypertension and antihypertensive medications are not well controlled. Some clinical symptoms or diseases of the heart that are not well controlled. History of immunodeficiency including HIV-positive. Subjects had active infections.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1210 + Apatinib +Fluzoparib<br>SHR-1210 will be administered as an intravenous infusion Apatinib tablets will be given orally Fluzoparib capsule will be given orally 28 days per cycle, until disease progression or unacceptable toxicity | Drug: SHR-1210 + Apatinib +Fluzoparib<br>* SHR-1210 will be administered as an intravenous infusion Apatinib tablets will be given orally Fluzoparib capsule will be given orally 28 days per cycle, until disease progression or unacceptable toxicity.<br>* Other names: Treatment group ： PD-1 antibody SHR-1210 combination with apatinib and fluzoparib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity (DLT) | Dose Limiting Toxicity | First cycle (28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events and Serious Adverse Events | AEs and SAEs | from the first drug administration to within 90 days for the last SHR-1210 dose | 
| Overall Response Rate (ORR) |  | up to 12 months (approx) from the start of treatment | 
| Duration of response (DoR) |  | up to 12 months (approx) from the start of treatment | 
| Disease Control Rate | DCR | up to 12 months (approx) from the start of treatment | 
| Progression-Free-Survival | PFS | up to 12 months (approx) from the start of treatment | 
| 12-months overall survival rate | 12-months overall survival rate | From the start of treatment to 1 year |