PD-1(Programmed Death-1) Antibody +GP as First Line Treatment for Triple Negative Breast Cancer(TNBC) Patients

April 19, 2022 updated by: Xichun Hu, Fudan University

Recombinant Humanized PD-1 Monoclonal Antibody (JS001) Combined With Gemcitabine and Cisplatin (GP) as First Line Treatment for Triple Negative Breast Cancer patients-a Phase 1 Clinical Trial

This is a Phase I dose escalation trial to assess dose-limiting toxicity (DLT) and MTD of JS001+GP in advanced/metastatic TNBC patients, and to determine the recommended Phase II dose and the best combination regimen.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

There will be 3 stages in this trial. Stage 1 is the dose escalation stage. JS001 will be tested in combination with GP in 3 dose levels.

Level 1: 120mg Level 2: 240mg Level 3: 480mg Patients will receive JS001+GP for 6 cycles and JS001 maintenance therapy for up to approximately 2 years.

JS001 will be given on d1 every 3 weeks with GP and every 2 weeks in maintenance therapy.

The first group of participants will receive the lowest dose level of JS001 at 120mg. Each new group will receive a higher dose of JS001 than the group before it until 480mg.

Stage 2 is the dose expansion stage. Dose expansion will be carried out to expand to 12 patients in the highest dose level at which the patient can tolerate well. This dose will also be recommended as phase 2 dose(RP2D).

Stage 3 is the sequential treatment stage. Patients receive 6 cycles of GP without JS001 and then receive JS001 maintenance therapy for up to approximately 2 years.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
31

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Shanghai, China, 200032
        • Fudan University Shanghai Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Histologically confirmed relapsed or metastatic triple negative breast cancer
  • Subjects must have normal organ and marrow function as defined below:
  • White blood cell ≥ 3,000/μL, Absolute neutrophil count ≥ 1,500/μL, Hemoglobin ≥ 9.0 g/dl, Platelet count ≥ 100,000/μL
  • Total bilirubin ≤1.25 X institutional upper limit of normal , aspartate aminotransferase(AST) ≤ 2.5 X institutional upper limit of normal, alanine transaminase(ALT) ≤ 2.5 X institutional upper limit of normal (For patients with liver metastasis, Total bilirubin ≤1.5 X institutional upper limit of normal , AST ≤5 X institutional upper limit of normal, ALT ≤5 X institutional upper limit of normal)
  • Serum creatinine within normal institutional limits
  • thyroid-stimulating hormone ,FT3(free triiodothyronine),FT4(Free thyroid hormone) within 0.9 X institutional lower limit of normal to 1.1 X institutional upper limit of normal (Except for patients who had thyroid ectomy)
  • Basically normal EKG and left ventricular ejection fraction(LVEF)>50%
  • Life expectancy of 6 months or more
  • Performance Status 0-1
  • Subjects must have at least one measurable disease per RECIST v1.1
  • Weight more than 45 Kilogram
  • Subjects must have not received chemotherapy in metastatic setting, subjects relapsed 6 months after the completion of adjuvant therapy are eligible
  • Subjects must be willing to supply fresh or archive tumor tissue for research purposes
  • Subjects must have stopped receiving any anti-cancer treatment (including chemotherapy, curative radiotherapy, and surgery or targeting therapy) for at least 4 weeks.
  • Subjects must have stopped receiving systemic immunosuppressive agents for at least 2 weeks.
  • Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Subjects with radiographically stable treated brain metastases are eligible but must not have been on steroid therapy for at least 4 weeks
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Gemcitabine, cisplatin or JS001
  • Patients who have adjuvant chemotherapy and relapsed within 6 months.
  • Pregnant or breastfeeding women are excluded from this study
  • Patients with HIV infection, patients with positive HbsAg or HCV(hepatitis C virus)-RNA
  • Patients with chronic autoimmune disease
  • Patients with prior therapy with antibodies that modulate T-cell function (e.g., anti-PD-1, anti-PD-L1, anti-CTLA-4(Cytotoxic T-lymphocyte-associated protein 4))
  • Patients with evidence of active, non-infectious pneumonia
  • Patients with a history of tuberculosis
  • Patients active infection requiring intravenous systemic therapy
  • Severe cardiovascular disease
  • Severe gastrointestinal dysfunction (bleeding, infection, obstruction or ≥ grade 1 diarrhea)
  • Patients with severe coagulation dysfunction or bleeding tendency, patients who are receiving thrombolysis or anticoagulation therapy
  • Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, severe hyper blood pressure, severe diabetes or severe thyroid disease that would limit compliance with study requirements
  • Patients with known psychiatric disorders that would interfere with cooperation with requirements of the trial
  • Patients who have received a vaccine within 4 weeks prior to the first dose of JS001
  • Patients with a known additional malignancy that is progressing or requires active treatment (within the last 5 years). Exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cancers that has undergone potentially curative therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: JS001 120mg+GP
Level 1: JS001 120mg +GP q3w,*6 cycles, then JS001 120mg q3w for maintenance therapy for up to approximately 2 years.
Combination product: JS001 120mg+GP
In this arm, JS001 120mg will be given at d1; Gem 1000mg/m2 d2,9; DDP(cisplatin) 75mg/m2 d2
Experimental: JS001 240mg+GP
Level 2: JS001 240mg +GP q3w,*6 cycles, then JS001 240mg q3w for maintenance therapy for up to approximately 2 years.
Combination product: JS001 240mg+GP
In this arm, JS001 240mg will be given at d1; Gem 1000mg/m2 d2,9; DDP 75mg/m2 d2
Experimental: JS001 480mg +GP
Level 3: JS001 480mg+GP q3w,*6 cycles, then JS001 480mg q3w for maintenance therapy for up to approximately 2 years.
Combination product: JS001 480mg+GP
In this arm, JS001 480mg will be given at d1; Gem 1000mg/m2 d2,9; DDP 75mg/m2 d2
Experimental: GP followed by JS001
sequential treatment: Patients receive 6 cycles of GP without JS001 and then receive JS001 maintenance therapy for up to approximately 2 years. JS001 will be given at RP2D.
Combination product: GP followed by JS001
In this arm,Patients receive 6 cycles of GP without JS001 and then receive JS001 maintenance therapy for up to approximately 2 years. JS001 will be given at RP2D.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) of JS001 when combined with GP
Time Frame: 3 weeks
If 1/6 patients has grade 3 or higher toxicity then escalation proceeds, if 2/6 has grade 3 or greater toxicity then this is declared MTD.
3 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Peak Plasma Concentration (Cmax)
Time Frame: 85 days
Cmax of JS001
85 days
Area under the plasma concentration versus time curve (AUC)
Time Frame: 85 days
AUC of JS001
85 days
other pharmacokinetics(PK) characteristics of JS001+GP
Time Frame: 85 days
half life of JS001
85 days
Incidence of Treatment-Emergent Adverse Events
Time Frame: 85 days
Incidence of Adverse Events that need to be treated immediately
85 days
Incidence of Severe Adverse Events
Time Frame: 85 days
Incidence of Adverse Events that cause hospitalization, inability, death, etc
85 days
objective response rate of JS001+GP
Time Frame: 1 year
objective response rate(%) is the sum of CR(complete remission) rate and PR(partial remission) rate
1 year
disease control rate of JS001+GP
Time Frame: 1 year
disease control rate(%) is the sum of CR rate and PR rate and SD(stable disease) rate for more than 6 weeks
1 year
duration of regression of JS001+GP
Time Frame: 1 year
duration of regression(months) is the time interval from randomization to disease progression
1 year
time to regression of JS001+GP
Time Frame: 1 year
time to regression(months) is the time interval from randomization to disease regressin
1 year
progression free survival of JS001+GP
Time Frame: 1 year
progression free survival(months) is the time interval from randomization to disease progression or death from any reason
1 year
overall survival of JS001+GP
Time Frame: 1 year
overall survival(months) is the time interval between randomization and death from any reason
1 year
best combination regimen
Time Frame: 1 year
Is JS001 combined with GP or GP followed by JS001 better in safety (incidence of grade 3-4 toxicity) and efficacy(Response Rate and PFS)
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fudan University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Xichun Hu, MD& PhD, Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 15, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 7, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 12, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 16, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 20, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Fudan-P1-201701

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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