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

Triple Negative Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT03777579
• Other study ID #: NABP201801
• Status: Suspended
• Phase: Phase 3
• Start date: December 21, 2018
• Est. completion date: July 30, 2020

Study information

• Verified date: December 2018
• Source: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 375
• Est. completion date: July 30, 2020
• Est. primary completion date: December 30, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
China	The fifth medical center of PLA general hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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.
Secondary	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.
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)