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

NCT03777579

Description:

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).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of First-line JS001 and Nab-paclitaxel Versus Palcelbo and Nab-Paclitaxel in Participants With Advanced Recurrent or Metastatic TNBC (KEYSTONE)
  • 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 IDs

  • ORG STUDY ID: NABP201801
  • NCT ID: NCT03777579

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
JS001,an engineered anti-PD-1 antibodyTerepril monoclonal antibodyJS001 Plus Nab-Paclitaxel
Nab-PaclitaxelPaclitaxel For Injection(Albumin Bound)JS001 Plus Nab-Paclitaxel
PlaceboPlacebo Plus Nab-Paclitaxel

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
JS001 Plus Nab-PaclitaxelExperimentalParticipants assigned to JS001 plus nab-paclitaxel will receive both agents until disease progression or unacceptable toxicity.
  • JS001,an engineered anti-PD-1 antibody
  • Nab-Paclitaxel
Placebo Plus Nab-PaclitaxelPlacebo ComparatorParticipants assigned to placebo plus nab-paclitaxel will receive both agents until disease progression or unacceptable toxicity.
  • Nab-Paclitaxel
  • Placebo

Eligibility Criteria

        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.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

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

Measure:Progression-Free Survival (PFS) Assessed Using RECIST v1.1 by investigator
Time Frame:From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 30 months)
Safety Issue:
Description: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.
Measure:Objective response rate (ORR) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)by IRC
Time Frame:From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 30 months)
Safety Issue:
Description:ORR is defined as the rate of CR or PR, as determined by IRC using RECIST v1.1 criteria.
Measure:Duration of response (DoR) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)by IRC
Time Frame:From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 30 months)
Safety Issue:
Description: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.
Measure:Disease control rate (DCR) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)by IRC
Time Frame:From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 30 months)
Safety Issue:
Description:DCR is defined as the rate of of CR, PR, or stable disease according to RECIST v1.1.
Measure:Overall Survival (OS)
Time Frame:From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months)
Safety Issue:
Description:OS is defined as the time from randomization to death from any cause.
Measure:OS rate at 12 months
Time Frame:the percent of participants that are alive at 12months from Day 1.
Safety Issue:
Description:OS is defined as the time from randomization to death from any cause.
Measure:OS rate at 24 months
Time Frame:the percent of participants that are alive at 24 months from Day 1.
Safety Issue:
Description:OS is defined as the time from randomization to death from any cause.
Measure:PFS Assessed Using immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) by investigator
Time Frame:From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months)
Safety Issue:
Description: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.
Measure:ORR Assessed Using immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) by investigator
Time Frame:From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months)
Safety Issue:
Description:ORR is defined as the rate of iCR or iPR, as determined by investigator using iRECIST criteria.
Measure:DoR Assessed Using immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) by investigator
Time Frame:From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months)
Safety Issue:
Description: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.
Measure:DCR Assessed Using immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) by investigator
Time Frame:From Day 1 to death from any cause, assessed up to end of study (up to approximately 30 months)
Safety Issue:
Description:DCR is defined as the rate of of iCR, iPR, or stable disease according to iRECIST.
Measure:Percentage and severity of Participants With Adverse Events (AEs)
Time Frame:From Day 1 to 60 days after last dose of study drug, assessed up to end of study (up to approximately 30 months)
Safety Issue:
Description:percentage and CTC AE(v5.0) of AEs
Measure:Percentage of Participants With Anti-Drug Antibodies (ATAs)
Time Frame: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)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

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