Toripalimab in Combination With Nab-Paclitaxel For Patients With Metastatic or Recurrent Triple-Negative Breast Cancer (TNBC) With or Without Systemic Treatment

Study Overview
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Brief Summary
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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).

Official Title
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A Randomized, Double-Blind, Multicenter, Phase III Study of Toripalimab(JS001) in Combination With Nab-Paclitaxel Versus Placebo Plus Nab-Paclitaxel for Patients With Metastatic or Recurrent Triple-Negative Breast Cancer With or Without Systemic Treatment (TORCHLIGHT)

Conditions
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Triple-Negative Breast Cancer

Intervention / Treatment
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* Drug: JS001
* Drug: Nab-Paclitaxel
* Drug: Placebo
* Drug: Nab-Paclitaxel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JS001 Plus Nab-Paclitaxel<br>Patients will receive both JS001 and Nab-Paclitaxel. | Drug: JS001<br>* JS001 240mg, i.v., q3w; Other name: Toripalimab<br>Drug: Nab-Paclitaxel<br>* Nab-Paclitaxel 125 mg/m2, i.v., d1, d8, q3w<br>|
| Placebo Comparator: Placebo Plus Nab-Paclitaxel<br>Patients will receive both placebo and Nab-Paclitaxel. | Drug: Placebo<br>* Placebo, i.v., q3w;<br>Drug: Nab-Paclitaxel<br>* Nab-Paclitaxel 125 mg/m2, i.v., d1, d8, q3w<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | Up to approximately 61 months from first patient in. | 
| PFS assessed by BICR using RECIST v1.1 in PD-L1 positive patients | 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. | Up to approximately 61 months from first patient in. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) assessed by investigator using RECIST v1.1. Analyzing among PD-L1 positive patients and Intend to Treat (ITT) respectively. | 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. | Up to approximately 61 months from first patient in. | 
| 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. | ORR is defined as the rate of CR(Complete Response) or PR (Partial Response), as determined by BICR using RECIST v1.1 | Up to approximately 61 months from first patient in. | 
| 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. | 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. | Up to approximately 61 months from first patient in. | 
| 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. | DCR is defined as the sum rate of CR, PR and SD (Stable Disease), as determined by BICR or investigators using RECIST v1.1 | Up to approximately 61 months from first patient in. | 
| Overall Survival (OS). Analyzing among PD-L1 positive patients and Intend to Treat (ITT) respectively. | OS is defined as the time from randomization to death from any cause | Up to approximately 61 months from first patient in. | 
| OS rate at 12 months. Analyzing among PD-L1 positive patients and Intend to Treat (ITT) respectively. | OS is defined as the time from randomization to death from any cause. | Up to approximately 61 months from first patient in. | 
| OS rate at 24 months. Analyzing among PD-L1 positive patients and Intend to Treat (ITT) respectively. | OS is defined as the time from randomization to death from any cause | Up to approximately 61 months from first patient in. | 
| 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 61months） | From Day 1 to death from any cause, assessed up to end of study (up to approximately 46 months） | 
| 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. | Evaluated by Eastern Cooperative Oncogloy Group (ECOG) Performance Status | From Day 1 to death from any cause, assessed up to end of study (up to approximately 61months) |