Clinical trial NCT04335006: 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.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Breast Cancer
Triple Negative Breast Cancer
Keywords: SHR-1210
PD-1
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-04-06
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 42 months)
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 42 months
measure: Overall Survival (OS) in PD-L1 positive/ITT population
timeFrame: Up to approximately 42 months
measure: Objective response rate (ORR) in the PD-L1-positive/ITT population
timeFrame: Up to approximately 42 months
measure: 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
timeFrame: Up to approximately 42 months
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Up to approximately 42 months
measure: Serum concentration of SHR-1210 and plasma concentration of apatinib
timeFrame: Up to approximately 42 months
measure: Proportion of anti-SHR-1210 antibody (ADA) and neutralizing antibody (Nab) formed during the study from baseline
timeFrame: Up to approximately 42 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
Study officials:
References: