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)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 531
- Locations
- 55
- Primary Endpoint
- 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.
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts 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.
Arms & Interventions
JS001 Plus Nab-Paclitaxel
Patients will receive both JS001 and Nab-Paclitaxel.
Intervention: Nab-Paclitaxel (Drug)
Placebo Plus Nab-Paclitaxel
Patients will receive both placebo and Nab-Paclitaxel.
Intervention: Placebo (Drug)
JS001 Plus Nab-Paclitaxel
Patients will receive both JS001 and Nab-Paclitaxel.
Intervention: JS001 (Drug)
Placebo Plus Nab-Paclitaxel
Patients will receive both placebo and Nab-Paclitaxel.
Intervention: Nab-Paclitaxel (Drug)
Outcomes
Primary Outcomes
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.
Time Frame: 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
Time Frame: 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 Outcomes
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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 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 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.)
- 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）)
- 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))