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

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

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).

Study Overview

• Status: Suspended
• Conditions: Triple Negative Breast Cancer
• Intervention / Treatment: Drug: JS001，an engineered anti-PD-1 antibody; Drug: Nab-Paclitaxel; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 375
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • The Fifth Medical Center of PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. 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;
2. No prior chemotherapy or targeted systemic therapy for inoperable stage IV or metastatic TNBC；
3. Eligible for taxane monotherapy；
4. Eastern Cooperative Oncology Group performance status of 0 or 1；
5. Measurable disease as defined by RECIST v1.1；
6. Adequate hematologic and end-organ function。

Exclusion Criteria:

1. Known central nervous system (CNS) disease with active syndrome or untreated disease, except for treated asymptomatic CNS metastases；
2. History of autoimmune disease；
3. History of Anaphylaxis to PD-(L)1 antibody or CTLA-4 antibody or paclitaxel;
4. Prior allogeneic stem cell or solid organ transplantation;
5. Active hepatitis B or hepatitis C;
6. Positive of HIV antibody.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Investigators: Principal Investigator: JIANG ZE FEI, PHD, Beijing 302 Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2018
• Primary Completion (Anticipated): December 30, 2019
• Study Completion (Anticipated): July 30, 2020

Study Registration Dates

• First Submitted: December 12, 2018
• First Submitted That Met QC Criteria: December 13, 2018
• First Posted (Actual): December 17, 2018

Study Record Updates

• Last Update Posted (Actual): August 8, 2019
• Last Update Submitted That Met QC Criteria: August 6, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Antibodies; Immunoglobulins; Albumin-Bound Paclitaxel
• Other Study ID Numbers: NABP201801

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No