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

NCT03251313 | Unknown Phase 1 DMC

• 1 other identifier: Fudan-P1-201701
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of JS001 when combined with GP

  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 Outcomes (12)

• Peak Plasma Concentration (Cmax)

  85 days

• Area under the plasma concentration versus time curve (AUC)

  85 days

• other pharmacokinetics(PK) characteristics of JS001+GP

  85 days

• Incidence of Treatment-Emergent Adverse Events

  85 days

• Incidence of Severe Adverse Events

  85 days

Study Arms (4)

JS001 120mg+GP

EXPERIMENTAL

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

JS001 240mg+GP

EXPERIMENTAL

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

JS001 480mg +GP

EXPERIMENTAL

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

GP followed by JS001

EXPERIMENTAL

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

Interventions

JS001 120mg+GP COMBINATION_PRODUCT

In this arm, JS001 120mg will be given at d1; Gem 1000mg/m2 d2,9; DDP(cisplatin) 75mg/m2 d2

JS001 120mg+GP

JS001 240mg+GP COMBINATION_PRODUCT

In this arm, JS001 240mg will be given at d1; Gem 1000mg/m2 d2,9; DDP 75mg/m2 d2

JS001 240mg+GP

JS001 480mg+GP COMBINATION_PRODUCT

In this arm, JS001 480mg will be given at d1; Gem 1000mg/m2 d2,9; DDP 75mg/m2 d2

JS001 480mg +GP

GP followed by JS001 COMBINATION_PRODUCT

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.

GP followed by JS001

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Xichun Hu, MD& PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Department of Medical Oncology

Study Record Dates

• First Submitted: June 7, 2017
• First Posted: August 16, 2017
• Study Start: May 15, 2019
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2022
• Last Updated: April 20, 2022

Record last verified: 2022-04

Locations

CN (1)