A Study of First-line JS001 and Nab-paclitaxel Versus Palcelbo and Nab-Paclitaxel in Participants With Advanced Recurrent or Metastatic TNBC

Study Overview
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Brief Summary
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This multicenter, randomized, double-blind study will evaluate the efficacy, safety of JS001 administered with nab-paclitaxel compared with placebo in combination with nab-paclitaxel as first-line therapy in participants with primarily diagnosed stage IV and recurrent or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic breast cancer (mBC).

Official Title
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A Phase III, Multicenter, Randomized, Placebo-Controlled Study of JS001 (Anti-PD-1 Antibody) in Combination With Nab-Paclitaxel Compared With Placebo With Nab-Paclitaxel as First-line Therapy for Patients With Primarily Diagnose or Recurrent and Metastatic Triple-Negative Breast Cancer

Conditions
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Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: JS001，an engineered anti-PD-1 antibody
* Drug: Nab-Paclitaxel
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primarily diagnosed stage IV or recurrent and metastatic, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression; No prior chemotherapy or targeted systemic therapy for inoperable stage IV or metastatic TNBC； Eligible for taxane monotherapy； Eastern Cooperative Oncology Group performance status of 0 or 1； Measurable disease as defined by RECIST v1.1； Adequate hematologic and end-organ function。 Exclusion Criteria: Known central nervous system (CNS) disease with active syndrome or untreated disease, except for treated asymptomatic CNS metastases； History of autoimmune disease； History of Anaphylaxis to PD-(L)1 antibody or CTLA-4 antibody or paclitaxel; Prior allogeneic stem cell or solid organ transplantation; Active hepatitis B or hepatitis C; Positive of HIV antibody.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JS001 Plus Nab-Paclitaxel<br>Participants assigned to JS001 plus nab-paclitaxel will receive both agents until disease progression or unacceptable toxicity. | Drug: JS001，an engineered anti-PD-1 antibody<br>* JS001 at a fixed dose of 240 milligrams via intravenous (IV) infusion on Days 1 of each 21-day cycle until disease progression or unacceptable toxicity.<br>* Other names: Terepril monoclonal antibody;Drug: Nab-Paclitaxel<br>* Nab-Paclitaxel at a starting dose of 125mg per square meter via IV infusion on Days 1, 8 of each 21-day cycle. Nab-Paclitaxel will be administered until disease progression or unacceptable toxicity.<br>* Other names: Paclitaxel For Injection（Albumin Bound）;|
| Placebo Comparator: Placebo Plus Nab-Paclitaxel<br>Participants assigned to placebo plus nab-paclitaxel will receive both agents until disease progression or unacceptable toxicity. | Drug: Nab-Paclitaxel<br>* Nab-Paclitaxel at a starting dose of 125mg per square meter via IV infusion on Days 1, 8 of each 21-day cycle. Nab-Paclitaxel will be administered until disease progression or unacceptable toxicity.<br>* Other names: Paclitaxel For Injection（Albumin Bound）;Drug: Placebo<br>* Placebo administered via intravenous (IV) infusion on Days 1 of each 21-day cycle until disease progression or unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)by Independent Review Committee (IRC) | 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. | From Day 1 to disease progression (PD) or death from any cause, assessed up to end of study (up to approximately 30 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) Assessed Using RECIST v1.1 by investigator | 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. | From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 30 months) | 
| Objective response rate (ORR) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)by IRC | ORR is defined as the rate of CR or PR, as determined by IRC using RECIST v1.1 criteria. | From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 30 months) | 
| Duration of response (DoR) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)by IRC | DoR is defined as the time period from the date of initial CR or PR until the date of PD or death from any cause, whichever occurs first. | From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 30 months) | 
| Disease control rate (DCR) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)by IRC | DCR is defined as the rate of of CR, PR, or stable disease according to RECIST v1.1. | From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 30 months) | 
| Overall Survival (OS) | OS is defined as the time from randomization to death from any cause. | From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months) | 
| OS rate at 12 months | OS is defined as the time from randomization to death from any cause. | the percent of participants that are alive at 12months from Day 1. | 
| OS rate at 24 months | OS is defined as the time from randomization to death from any cause. | the percent of participants that are alive at 24 months from Day 1. | 
| PFS Assessed Using immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) by investigator | Progression is confirmed in the target lesion category if the next imaging assessment after iUPD (4-8 weeks later) confirms a further increase in sum of measures of target disease from iUPD, with an increase of at least 5mm. | From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months) | 
| ORR Assessed Using immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) by investigator | ORR is defined as the rate of iCR or iPR, as determined by investigator using iRECIST criteria. | From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months) | 
| DoR Assessed Using immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) by investigator | DoR is defined as the time period from the date of initial iCR or iPR until the date of iCPD or death from any cause, whichever occurs first. | From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months) | 
| DCR Assessed Using immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) by investigator | DCR is defined as the rate of of iCR, iPR, or stable disease according to iRECIST. | From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months) | 
| Percentage and severity of Participants With Adverse Events (AEs) | percentage and CTC AE(v5.0) of AEs | From Day 1 to 60 days after last dose of study drug, assessed up to end of study (up to approximately 30 months) | 
| Percentage of Participants With Anti-Drug Antibodies (ATAs) |  | Pre-dose (60minutes±10minutes) on Day 1 of Cycles 1, 3, 5, 7, 9 and at every 6 cycles thereafter until disease progression, at disease progression. (maximum up to 30 months) (1 Cycle = 21 days) |