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Study on TIL for the Treatment of Advanced Breast Cancer

Primary Purpose

Breast Cancer, Treatment Side Effects, Advanced Breast Cancer

Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
Tumor Infiltrating Lymphocytes (TIL)
Sponsored by
Shanghai Juncell Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Tumor Infiltrating Lymphocytes

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age: 18 years to 75 years;
  2. Histologically diagnosed as primary/relapsed/metastasized breast cancer;
  3. Expected life-span more than 3 months;
  4. Karnofsky≥60% or ECOG score 0-2;
  5. Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available.
  6. Test subjects must have tumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated;
  7. At least 1 evaluable tumor lesion;
  8. Hematology and Chemistry(within 7 days prior to enrollment):

    • Absolute count of white blood cells≥2.5×10^9/L;
    • Absolute count of neutropils≥1.5×10^9/L;
    • Absolute count of lymphocytes ≥0.7×109/L;
    • Platelet count≥100×10^9;
    • hemoglobin≥90 g/L;
    • Activated partial thromboplastin time (APTT) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days);
    • International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days);
    • Serum creatinine ≤1.5mg/dL(or ≤132.6μmol/L), or clearance rate≥50mL/min;
    • Serum ALT/AST ≤3×ULN(subjects with liver metastasis ≤3×ULN);
    • Totol bilirubin≤1.5×ULN;
  9. no absolute or relative contraindications to operation or biopsy;
  10. Test subjects with child-bearing potential must be willing to practice approved highly effective methods of contraception at the time of informed consent, and continue within 1 year after the completion of lymphodepletion;
  11. Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy and biologics must cease 28 days before obtaining TILs;
  12. Be able to understand and sign the informed consent document;
  13. Be able to stick to follow-up visit plan and other requirements in the agreement.

Exclusion Criteria:

  1. Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory treatment;
  2. Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of the lung for carbon monoxide (DLCO) (calibrated) less than 40%;
  3. Significant cardiovascular anomalies according to any of the following definition: New York Heart Association (NYHA) Grade III or IV congestive heart failure, clinically significant low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrio-ventricular conductive block, etc.
  4. Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, active HBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infection or Treponema pallidum antibody positive;
  5. Severe physical or mental diseases;
  6. Have a systemic active infection requiring treatment, or have positive blood cultures(or imaging evidence of infection);
  7. Having been treated within a month or being treated now with other medicines, or other biologic therapy, chemo-or radiotherapy;
  8. History of allergy to chemical compound consisting of chemical and biologic substances resembling cell therapy;
  9. Having received immunotherapy and developed irAE level greater than Level 3;
  10. Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below (toxicity considered by the investigator as non-safety concerns like alopecia excluded);
  11. Females in pregnancy or lactation;
  12. History of organ transplantation, allogeneic stem cell transplantation, and renal replacement therapy;
  13. Researchers considering the test subject as having a history of other severe systemic diseases, or other reasons inappropriate for the clinical study.

Sites / Locations

  • Shanghai Tenth People's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tumor Infiltrating Lymphocytes (TIL)

Arm Description

1x10^9-5x10^10 in vitro expanded autologous TILs will be infused i.v. to patients with advanced breast cancer after NMA lymphodepletion treatment with hydroxychloroquine(600mg,single-dose) and cyclophosphamide.

Outcomes

Primary Outcome Measures

Adverse Events (AE)
To characterize the safety profile of GC101 TIL in patients with advanced breast cancer as assessed by incidence of adverse events.
Objective Response Rate (ORR)
Proportion of patients with response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): ORR (proportion of patients) = # with CR + # with PR / # with CR + # with PR + # with SD + # with PD. ( Except baseline evaluation within 28 days before GC101 TIL infusion,PET/CT scan will be performed at 6 weeks after TIL infusion, and than every 6 weeks for 6 months, and then every 6 months after that for up to 3 years)
Disease Control Rate (DCR)
Percentage of patients that meet CR, PR and SD criteria set in this study according to RECIST v1.1: DCR (proportion of patients) = # with CR + # with PR + # with SD / # with CR + # with PR + # with SD + # with PD.
Duration of Response (DOR)
The time length between the first confirmed objective response per RECIST 1.1 to the treatment and the subsequent disease progression per RECIST 1.1
Progression-Free Survival (PFS)
The time length between GC101 TIL infusion and confirmed subsequent disease progression according to RECIST 1.1
Overall Survival (OS)
The length of time from the date of the start of GC101 TIL treatment that the patients are still alive

Secondary Outcome Measures

Change in Quality of Life
Comparison of patients' quality of life before and after GC101 TIL treatment as assessed by the EORTC QLQ-30 (V3.0).

Full Information

First Posted
November 24, 2021
Last Updated
December 19, 2022
Sponsor
Shanghai Juncell Therapeutics
Collaborators
Shanghai 10th People's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05142475
Brief Title
Study on TIL for the Treatment of Advanced Breast Cancer
Official Title
A Clinical Study on TIL for the Treatment of Advanced Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 19, 2021 (Actual)
Primary Completion Date
December 20, 2023 (Anticipated)
Study Completion Date
December 20, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Juncell Therapeutics
Collaborators
Shanghai 10th People's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This study is to investigate the safety and efficacy of tumor infiltrating lymphocyte (TIL) therapy (GC 101 TIL) in patients with advanced breast cancer. Autologous TILs are expanded from tumor resections or biopsies and infused i.v. into the patient after NMA lymphodepletion treatment with hydroxychloroquine(600mg,single-dose) and cyclophosphamide.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Treatment Side Effects, Advanced Breast Cancer, Effects of Immunotherapy
Keywords
Tumor Infiltrating Lymphocytes

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tumor Infiltrating Lymphocytes (TIL)
Arm Type
Experimental
Arm Description
1x10^9-5x10^10 in vitro expanded autologous TILs will be infused i.v. to patients with advanced breast cancer after NMA lymphodepletion treatment with hydroxychloroquine(600mg,single-dose) and cyclophosphamide.
Intervention Type
Biological
Intervention Name(s)
Tumor Infiltrating Lymphocytes (TIL)
Intervention Description
Adoptive transfer of 1x10^9-5x10^10 autologous TILs to patients i.v. in 30-120 minutes.
Primary Outcome Measure Information:
Title
Adverse Events (AE)
Description
To characterize the safety profile of GC101 TIL in patients with advanced breast cancer as assessed by incidence of adverse events.
Time Frame
6 months
Title
Objective Response Rate (ORR)
Description
Proportion of patients with response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): ORR (proportion of patients) = # with CR + # with PR / # with CR + # with PR + # with SD + # with PD. ( Except baseline evaluation within 28 days before GC101 TIL infusion,PET/CT scan will be performed at 6 weeks after TIL infusion, and than every 6 weeks for 6 months, and then every 6 months after that for up to 3 years)
Time Frame
Up to 36 months
Title
Disease Control Rate (DCR)
Description
Percentage of patients that meet CR, PR and SD criteria set in this study according to RECIST v1.1: DCR (proportion of patients) = # with CR + # with PR + # with SD / # with CR + # with PR + # with SD + # with PD.
Time Frame
Up to 36 months
Title
Duration of Response (DOR)
Description
The time length between the first confirmed objective response per RECIST 1.1 to the treatment and the subsequent disease progression per RECIST 1.1
Time Frame
Up to 36 months
Title
Progression-Free Survival (PFS)
Description
The time length between GC101 TIL infusion and confirmed subsequent disease progression according to RECIST 1.1
Time Frame
Up to 36 months
Title
Overall Survival (OS)
Description
The length of time from the date of the start of GC101 TIL treatment that the patients are still alive
Time Frame
Up to 36 months
Secondary Outcome Measure Information:
Title
Change in Quality of Life
Description
Comparison of patients' quality of life before and after GC101 TIL treatment as assessed by the EORTC QLQ-30 (V3.0).
Time Frame
Up to 36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age: 18 years to 75 years; Histologically diagnosed as primary/relapsed/metastasized breast cancer; Expected life-span more than 3 months; Karnofsky≥60% or ECOG score 0-2; Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available. Test subjects must have tumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated; At least 1 evaluable tumor lesion; Hematology and Chemistry(within 7 days prior to enrollment): Absolute count of white blood cells≥2.5×10^9/L; Absolute count of neutropils≥1.5×10^9/L; Absolute count of lymphocytes ≥0.7×109/L; Platelet count≥100×10^9; hemoglobin≥90 g/L; Activated partial thromboplastin time (APTT) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days); International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days); Serum creatinine ≤1.5mg/dL(or ≤132.6μmol/L), or clearance rate≥50mL/min; Serum ALT/AST ≤3×ULN(subjects with liver metastasis ≤3×ULN); Totol bilirubin≤1.5×ULN; no absolute or relative contraindications to operation or biopsy; Test subjects with child-bearing potential must be willing to practice approved highly effective methods of contraception at the time of informed consent, and continue within 1 year after the completion of lymphodepletion; Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy and biologics must cease 28 days before obtaining TILs; Be able to understand and sign the informed consent document; Be able to stick to follow-up visit plan and other requirements in the agreement. Exclusion Criteria: Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory treatment; Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of the lung for carbon monoxide (DLCO) (calibrated) less than 40%; Significant cardiovascular anomalies according to any of the following definition: New York Heart Association (NYHA) Grade III or IV congestive heart failure, clinically significant low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrio-ventricular conductive block, etc. Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, active HBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infection or Treponema pallidum antibody positive; Severe physical or mental diseases; Have a systemic active infection requiring treatment, or have positive blood cultures(or imaging evidence of infection); Having been treated within a month or being treated now with other medicines, or other biologic therapy, chemo-or radiotherapy; History of allergy to chemical compound consisting of chemical and biologic substances resembling cell therapy; Having received immunotherapy and developed irAE level greater than Level 3; Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below (toxicity considered by the investigator as non-safety concerns like alopecia excluded); Females in pregnancy or lactation; History of organ transplantation, allogeneic stem cell transplantation, and renal replacement therapy; Researchers considering the test subject as having a history of other severe systemic diseases, or other reasons inappropriate for the clinical study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
GC Clinical
Phone
086-18001759113
Email
clinicaltrials@juncell.com
Facility Information:
Facility Name
Shanghai Tenth People's Hospital
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qing Xu
Email
xuqingmd@aliyun.com

12. IPD Sharing Statement

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Study on TIL for the Treatment of Advanced Breast Cancer

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