A Phase 3 Study Comparing Carelizumab Plus Nab-paclitaxel and Apatinib, Carelizumab Plus Nab-paclitaxel, and Nab-paclitaxel in Patients With Advanced Triple Negative Breast Cancer.

Study Overview
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Brief Summary
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This randomized, open-label phase 3 study will evaluate the safety and efficacy of Carelizumab (an engineered anti-programmed death-ligand 1 [PD-1] antibody) in combination with Nab-paclitaxel and Apatinib, carelizumab plus nab-paclitaxel, and Nab-paclitaxel in Patients with Unresectable Locally Advanced or Metastatic Triple Negative Breast Cancer. Participants will be randomized in a 1:1:1 ratio to Arm A (Carelizumab + Nab-paclitaxel + Apatinib), Arm B (Carelizumab + Nab-paclitaxel), or Arm C (Nab-paclitaxel).

Official Title
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A Multicentre, Open-parallel, Randomized, Controlled Phase Ⅲ Study Comparing Carelizumab Plus Nab-paclitaxel and Apatinib, Carelizumab Plus Nab-paclitaxel, and Nab-paclitaxel in Patients With Unresectable Locally Advanced or Metastatic Triple Negative Breast Cancer.

Conditions
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Breast Cancer, Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: Carelizumab
* Drug: Nab-paclitaxel
* Drug: Apatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ECOG Performance Status of 0-1. Expected lifetime of not less than three months Metastatic or locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression) Cancer stage: locally advanced or metastatic breast cancer; Locally advanced breast cancer not amenable to radical resection. No prior systemic antitumor therapy for metastatic triple-negative breast cancer. Adequate hematologic and organ function Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) Exclusion Criteria: Known central nervous system (CNS) disease. Previously received anti-VEGFR small molecule tyrosine kinase inhibitors or anti-PD-1/PD-L1 antibody. A history of bleeding, any serious bleeding events. Uncontrolled pleural effusion, pericardial effusion. Malignancies other than TNBC within 5 years prior to randomisation, or ascites requiring recurrent drainage procedures History of interstitial pneumonitis. Severe chronic or active infections in need of systemic antibacterial, antifungal, or antiviral treatment, including TB, etc. Prior allogeneic stem cell or solid organ transplantation. History of autoimmune disease Active hepatitis B or hepatitis C Pregnancy or lactation. Peripheral neuropathy grade ≥2. Participants with poor blood pressure control; Myocardial infarction incident within 6 months prior to randomisation; Treatment with systemic immunostimulatory agents within 4 weeks prior to randomisation Treatment with systemic immunosuppressive medications within 2 weeks prior to randomisation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental A<br>Subjects receive Carelizumab in combination with Nab-paclitaxel plus Apatinib,each 4-week cycle | Drug: Carelizumab<br>* Participants receive SHR-1210 intravenously (IV)<br>* Other names: SHR-1210;Drug: Nab-paclitaxel<br>* administered intravenously every 4-week cycle<br>Drug: Apatinib<br>* administered orally every 4-week cycle<br>|
| Experimental: Experimental B<br>Subjects receive Carelizumab in combination with Nab-paclitaxel,each 4-week cycle | Drug: Carelizumab<br>* Participants receive SHR-1210 intravenously (IV)<br>* Other names: SHR-1210;Drug: Nab-paclitaxel<br>* administered intravenously every 4-week cycle<br>|
| Active Comparator: Comparator C<br>Subjects receive nab-paclitaxel intravenously each 4-week cycle. | Drug: Nab-paclitaxel<br>* administered intravenously every 4-week cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Progression-free survival (PFS) as determined by the IRC according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in PD-L1 positive / ITT population | Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 42 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Progression Free Survival (PFS) as determined by the investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) in PD-L1 positive/ITT population | Up to approximately 42 months | 
| Overall Survival (OS) in PD-L1 positive/ITT population |  | Up to approximately 42 months | 
| Objective response rate (ORR) in the PD-L1-positive/ITT population |  | Up to approximately 42 months | 
| Clinical benefit rate (CBR), defined as the proportion of patients with a CR or a PR or stable disease as determined by the investigator according to RECIST 1.1 |  | Up to approximately 42 months | 
| Percentage of Participants with Adverse Events (AEs) |  | Up to approximately 42 months | 
| Serum concentration of SHR-1210 and plasma concentration of apatinib |  | Up to approximately 42 months | 
| Proportion of anti-SHR-1210 antibody (ADA) and neutralizing antibody (Nab) formed during the study from baseline |  | Up to approximately 42 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SHR-1210, PD-1