Breast Cancer, Triple Negative Breast Cancer
Conditions
Keywords
SHR-1210, PD-1
Brief summary
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).
Interventions
DRUGCarelizumab
Participants receive SHR-1210 intravenously (IV)
DRUGNab-paclitaxel
administered intravenously every 4-week cycle
DRUGApatinib
administered orally every 4-week cycle
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 42 months) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Progression Free Survival (PFS) | Up to approximately 42 months | 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 |
| 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 | — |
| Percentage of Participants with Adverse Events (AEs) | Up to approximately 42 months | — |
Countries
China
Outcome results
None listed