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.

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.

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).

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Triple Negative Breast Cancer
• Intervention / Treatment: Drug: Carelizumab; Drug: Nab-paclitaxel; Drug: Apatinib

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2020
• Primary Completion (Actual): April 14, 2023
• Study Completion (Actual): April 14, 2023

Study Registration Dates

• First Submitted: March 31, 2020
• First Submitted That Met QC Criteria: April 2, 2020
• First Posted (Actual): April 6, 2020

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 4, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: PD-1; SHR-1210
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Paclitaxel; Apatinib
• Other Study ID Numbers: SHR-1210-III-318

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No