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

Sponsor

CSPC ZhongQi Pharmaceutical Technology Co., Ltd. (Industry)

Overall Status

Suspended

CT.gov ID

NCT03777579

Collaborator

(none)

375

Enrollment

Location

Arms

19.3

Anticipated Duration (Months)

19.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Triple Negative Breast Cancer	Drug: JS001，an engineered anti-PD-1 antibody Drug: Nab-Paclitaxel Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

375 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 21, 2018

Anticipated Primary Completion Date :

Dec 30, 2019

Anticipated Study Completion Date :

Jul 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: JS001 Plus Nab-Paclitaxel 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 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. Other Names: Terepril monoclonal antibody Drug: Nab-Paclitaxel 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. Other Names: Paclitaxel For Injection（Albumin Bound）
Placebo Comparator: Placebo Plus Nab-Paclitaxel Participants assigned to placebo plus nab-paclitaxel will receive both agents until disease progression or unacceptable toxicity.	Drug: Nab-Paclitaxel 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. Other Names: Paclitaxel For Injection（Albumin Bound） Drug: Placebo Placebo administered via intravenous (IV) infusion on Days 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Arm

Intervention/Treatment

Experimental: JS001 Plus Nab-Paclitaxel

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

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.

Other Names:

Terepril monoclonal antibody

Drug: Nab-Paclitaxel

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.

Other Names:

Paclitaxel For Injection（Albumin Bound）

Placebo Comparator: Placebo Plus Nab-Paclitaxel

Participants assigned to placebo plus nab-paclitaxel will receive both agents until disease progression or unacceptable toxicity.

Drug: Nab-Paclitaxel

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.

Other Names:

Paclitaxel For Injection（Albumin Bound）

Drug: Placebo

Placebo administered via intravenous (IV) infusion on Days 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Progression-Free Survival (PFS) Assessed Using RECIST v1.1 by investigator [From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 30 months)]
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.
Objective response rate (ORR) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)by IRC [From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 30 months)]
ORR is defined as the rate of CR or PR, as determined by IRC using RECIST v1.1 criteria.
Duration of response (DoR) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)by IRC [From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 30 months)]
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.
Disease control rate (DCR) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)by IRC [From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 30 months)]
DCR is defined as the rate of of CR, PR, or stable disease according to RECIST v1.1.
Overall Survival (OS) [From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months)]
OS is defined as the time from randomization to death from any cause.
OS rate at 12 months [the percent of participants that are alive at 12months from Day 1.]
OS is defined as the time from randomization to death from any cause.
OS rate at 24 months [the percent of participants that are alive at 24 months from Day 1.]
OS is defined as the time from randomization to death from any cause.
PFS Assessed Using immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) by investigator [From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months)]
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.
ORR Assessed Using immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) by investigator [From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months)]
ORR is defined as the rate of iCR or iPR, as determined by investigator using iRECIST criteria.
DoR Assessed Using immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) by investigator [From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months)]
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.
DCR Assessed Using immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) by investigator [From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months)]
DCR is defined as the rate of of iCR, iPR, or stable disease according to iRECIST.
Percentage and severity of Participants With Adverse Events (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 and CTC AE(v5.0) of AEs
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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.