Triple-Negative Breast Cancer
Conditions
Brief summary
This multicenter, randomized, double-blind study will evaluate the efficacy and safety of Toripalimab (JS001) combined with nab-paclitaxel compared with placebo combined with nab-paclitaxel for first/second line treatment of metastatic or recurrent triple-negative breast cancer (TNBC).
Interventions
DRUGJS001
JS001 240mg, i.v., q3w; Other name: Toripalimab
DRUGNab-Paclitaxel
Nab-Paclitaxel 125 mg/m2, i.v., d1, d8, q3w
DRUGPlacebo
Placebo, i.v., q3w;
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Metastatic or recurrent triple negative breast cancer (TNBC); * Histologically confirmed diagnosis of TNBC characterized by estrogen-receptor negative (ER-), progesterone receptor negative (PR-) and human epidermal growth factor-2 receptor negative (HER2-); * Eligible for taxane monotherapy; * No more than one line of chemotherapy in metastatic setting; * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; * Life expectancy of 12 weeks or more; * At least one measurable lesion per RECIST v1.1; * Demonstrate adequate hematologic and organ functions as defined in the protocol
Exclusion criteria
Prior treatment with taxane as first line treatment; * Prior treatment with PD-1 antibody, PD-L1 antibody, PD-L2 antibody, or CTLA4 antibody (or any other antibody acting on T cell co-stimulation or checkpoint pathway) * MRI assessment during screening or previous imaging studies confirmed active or untreated brain metastases. Patients previously treated with local treatment of brain metastases has been stable for ≥ 1 month, and have stopped systemic hormonal therapy (\>10 mg/d prednisone or equivalent) \> 4 weeks before randomization can participate in the study; * Meningeal carcinomatosis; * Pregnancy or lactation; * Active hepatitis B or hepatitis C.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Intend to Treat patients. | Up to approximately 61 months from first patient in. | PFS is defined as the time from randomization to the first occurrence of PD, as determined by the BIRC using RECIST v1.1, or death from any cause during the study, whichever occurs first. PD is defined as greater than or equal to (\>/=) 20 percent (%) relative increase and \>/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. |
| PFS assessed by BICR using RECIST v1.1 in PD-L1 positive patients | Up to approximately 61 months from first patient in. | PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator using RECIST v1.1, or death due to any cause during the study, whichever occurs first. PD is defined as greater than or equal to (\>/=) 20 percent (%) relative increase and \>/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DoR) assessed by BICR or investigators using RECIST v1.1. Analyzing among PD-L1 positive patients and Intend to Treat (ITT) respectively. | Up to approximately 61 months from first patient in. | DoR is defined as the time period from the date of initial CR or PR until the date of PD or death due to any cause, whichever occurs first. |
| Disease control rate (DCR) assessed by BICR or investigators using RECIST v1.1. Analyzing among PD-L1 positive patients and Intend to Treat (ITT) respectively. | Up to approximately 61 months from first patient in. | DCR is defined as the sum rate of CR, PR and SD (Stable Disease), as determined by BICR or investigators using RECIST v1.1 |
| Overall Survival (OS). Analyzing among PD-L1 positive patients and Intend to Treat (ITT) respectively. | Up to approximately 61 months from first patient in. | OS is defined as the time from randomization to death from any cause |
| Progression-Free Survival (PFS) assessed by investigator using RECIST v1.1. Analyzing among PD-L1 positive patients and Intend to Treat (ITT) respectively. | Up to approximately 61 months from first patient in. | PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first. PD is defined as greater than or equal to (\>/=) 20 percent (%) relative increase and \>/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. |
| OS rate at 24 months. Analyzing among PD-L1 positive patients and Intend to Treat (ITT) respectively. | Up to approximately 61 months from first patient in. | OS is defined as the time from randomization to death from any cause |
| Differences in safety and tolerability as assessed by the occurrence of adverse events. Analyzing among PD-L1 positive patients and Intend to Treat (ITT) respectively. | From Day 1 to death from any cause, assessed up to end of study (up to approximately 46 months） | From Day 1 to death from any cause, assessed up to end of study (up to approximately 61months） |
| Differences in the scores of disease/treatment-related symptoms evaluted by ECOG Performance Status. Analyzing among PD-L1 positive patients and Intend to Treat (ITT) respectively. | From Day 1 to death from any cause, assessed up to end of study (up to approximately 61months) | Evaluated by Eastern Cooperative Oncogloy Group (ECOG) Performance Status |
| OS rate at 12 months. Analyzing among PD-L1 positive patients and Intend to Treat (ITT) respectively. | Up to approximately 61 months from first patient in. | OS is defined as the time from randomization to death from any cause. |
| Objective response rate (ORR) assessed by BICR or investigators using RECIST v1.1. Analyzing among PD-L1 positive patients and Intend to Treat (ITT) respectively. | Up to approximately 61 months from first patient in. | ORR is defined as the rate of CR(Complete Response) or PR (Partial Response), as determined by BICR using RECIST v1.1 |
Countries
China
Outcome results
None listed