EGFR/B7H3 CAR-T on Lung Cancer and Triple Negative Breast Cancer
Primary Purpose
EGFR/ B7H3-positive Advanced Lung Cancer, EGFR/ B7H3-positive Advanced Triple-negative Breast Cancer
Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
EGFR/B7H3 CAR-T
Sponsored by
About this trial
This is an interventional treatment trial for EGFR/ B7H3-positive Advanced Lung Cancer
Eligibility Criteria
Inclusion Criteria:
- 1.All subjects or legal guardians must sign the informed consent form approved by the ethics committee in writing before starting any screening procedure;
- 2.18 Years to 75 Years, Histologically or cytologically confirmed Routine treatment of patients with advanced lung cancer and triple-negative breast cancer(Including TKI treatment failure patients);
- 3.EGFR/B7H3 expression was confirmed positive in tumor site by immunohistochemical test within 3 months before signing the informed consent form;
- 4.According to RECIST version 1.1 of solid tumor efficacy evaluation criteria, there should be at least one measurable lesion during screening period (results are available within one month prior to screening period) ;
- 5.Expected survival time ≥ 12 weeks;
- 6.The Eastern oncology group strength status score (ECOG) was 0-1;
- 7.Adequate organ function: alanine aminotransferase, aspartate aminotransferase (ALT, AST) < 3 times of normal value, total bilirubin (TBiL) < 1.5 times of normal value, serum creatinine (SCr) < 1.5 times of normal value;
- 8.The hemodynamics determined by echocardiography or multichannel radionuclide angiography(MUGA) are stable and the left ventricular ejection fraction (LVEF)≥50%;
- 9.Have sufficient bone marrow reserves (subjects can meet this requirement through blood transfusion), defined as: The number of white blood cells should not be less than 1 × 10^9/L;Platelet≥100 x 10^9/L; Hemoglobin ≥100 g/L;
- 10.Women of childbearing age and all male subjects must agree to use effective contraceptive methods for at least 52 weeks after EGFR CAR-T infusion, and until two consecutive PCR tests show that CAR-T cells are no longer present in the body.
Exclusion Criteria:
- 1.Uncontrolled hypertension (> 160/95), unstable coronary artery disease confirmed by uncontrolled arrhythmia, unstable angina pectoris, decompensated congestive heart failure (> New York Heart Association Class II), or myocardial infarction within 6 months prior to cell infusion;
- 2.Patients with severe liver and kidney dysfunction or consciousness disorder;
- 3.Patients who received antitumor chemotherapy other than lymphocyte clearance chemotherapy within 14 days prior to CAR T infusion;
- 4.Patients who received other study drugs within 14 days prior to infusion;
- 5. Patients treated with radiotherapy or TKI within 2 weeks prior to infusion;
- 6. Patients with active hepatitis B: HBV DNA>1000IU/mL;
- 7. HIV antibody, hepatitis C antibody, treponema pallidum antibody positive patients;
- 8. Sputum smears and patients who test positive for T cells of tuberculosis infection
- 9.Patients with interstitial lung disease or pneumonia;
- 10.patients with uncontrolled acute life-threatening bacterial, viral or fungal infection (e.g. positive blood culture ≤72 hours prior to infusion);
- 11.Patients with central nervous primary tumor or central metastasis solid tumor (patients with stable treatment for more than 4 weeks after brain metastasis or patients with asymptomatic brain metastasis without treatment are excluded from this range), and patients with pericardial metastasis accompanied by large pericardial effusion.
12.Patients with a prior or concurrent second tumor, except in the following cases:
- Adequately treated basal cell or squamous cell carcinoma (adequate wound healing required prior to enrollment);
- Carcinoma in situ of cervical or breast cancer with no signs of recurrence for at least 3 years prior to study after curative treatment;
- The primary malignancy has been completely resected and in complete remission for ≥5 years.
- 13.Pregnant or lactating women;
- 14.Patients who have a history of or currently have T-cell tumors;
- 15. have active neuroautoimmune or inflammatory disorders (e.g. Guillian-Barre syndrome, AMyotrophic lateral sclerosis);
- 16.Other conditions, such as compliance, that the investigator considers should not be included in this clinical trial.
Sites / Locations
- Second Affiliated Hospital of Guangzhou Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment
Arm Description
Patients will receive 2*10e6/kgCAR-T cells.
Outcomes
Primary Outcome Measures
Safety by Common Terminology Criteria for Adverse Events (CTCAE) V5.0
The type, frequency, severity, and duration of adverse events as a result of EGFR/B7H3 CAR-T cells infusion will be summarized
Secondary Outcome Measures
Objective Response Rate (ORR)
Per Response Evaluation Criteria in Solid Tumours (RECIST 1.1) assessed by MRI or CT. ORR is the percentage of patients at Complete Response (CR) or Partial Response (PR) (according to independent review), prior to progression or further anti-cancer therapy
Full Information
NCT ID
NCT05341492
First Posted
April 18, 2022
Last Updated
February 26, 2023
Sponsor
Second Affiliated Hospital of Guangzhou Medical University
1. Study Identification
Unique Protocol Identification Number
NCT05341492
Brief Title
EGFR/B7H3 CAR-T on Lung Cancer and Triple Negative Breast Cancer
Official Title
A Single-arm, Open, Exploratory Clinical Study Evaluating the Safety and Efficacy of EGFR/B7H3 CAR-T in Patients With EGFR/ B7H3-positive Advanced Solid Tumors (Lung and Triple-negative Breast Cancer)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2022 (Actual)
Primary Completion Date
May 1, 2025 (Anticipated)
Study Completion Date
May 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital of Guangzhou Medical University
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 a single-arm, open, exploratory clinical study to evaluate the safety and efficacy of EGFR/B7H3 CAR-T in patients with EGFR/ B7H3-positive advanced solid tumors (lung cancer and triple-negative breast cancer)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
EGFR/ B7H3-positive Advanced Lung Cancer, EGFR/ B7H3-positive Advanced Triple-negative Breast Cancer
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
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Experimental
Arm Description
Patients will receive 2*10e6/kgCAR-T cells.
Intervention Type
Biological
Intervention Name(s)
EGFR/B7H3 CAR-T
Intervention Description
2 × 10^6/kg CAR-T cells,For subjects with body weight greater than 60 kg, the number of cells can only be calculated according to 60 kg of body weight.
Primary Outcome Measure Information:
Title
Safety by Common Terminology Criteria for Adverse Events (CTCAE) V5.0
Description
The type, frequency, severity, and duration of adverse events as a result of EGFR/B7H3 CAR-T cells infusion will be summarized
Time Frame
In CAR-T cells infusion, up to 52 weeks.
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
Per Response Evaluation Criteria in Solid Tumours (RECIST 1.1) assessed by MRI or CT. ORR is the percentage of patients at Complete Response (CR) or Partial Response (PR) (according to independent review), prior to progression or further anti-cancer therapy
Time Frame
In CAR-T cells infusion, up to 52 weeks.
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:
1.All subjects or legal guardians must sign the informed consent form approved by the ethics committee in writing before starting any screening procedure;
2.18 Years to 75 Years, Histologically or cytologically confirmed Routine treatment of patients with advanced lung cancer and triple-negative breast cancer(Including TKI treatment failure patients);
3.EGFR/B7H3 expression was confirmed positive in tumor site by immunohistochemical test within 3 months before signing the informed consent form;
4.According to RECIST version 1.1 of solid tumor efficacy evaluation criteria, there should be at least one measurable lesion during screening period (results are available within one month prior to screening period) ;
5.Expected survival time ≥ 12 weeks;
6.The Eastern oncology group strength status score (ECOG) was 0-1;
7.Adequate organ function: alanine aminotransferase, aspartate aminotransferase (ALT, AST) < 3 times of normal value, total bilirubin (TBiL) < 1.5 times of normal value, serum creatinine (SCr) < 1.5 times of normal value;
8.The hemodynamics determined by echocardiography or multichannel radionuclide angiography(MUGA) are stable and the left ventricular ejection fraction (LVEF)≥50%;
9.Have sufficient bone marrow reserves (subjects can meet this requirement through blood transfusion), defined as: The number of white blood cells should not be less than 1 × 10^9/L;Platelet≥100 x 10^9/L; Hemoglobin ≥100 g/L;
10.Women of childbearing age and all male subjects must agree to use effective contraceptive methods for at least 52 weeks after EGFR CAR-T infusion, and until two consecutive PCR tests show that CAR-T cells are no longer present in the body.
Exclusion Criteria:
1.Uncontrolled hypertension (> 160/95), unstable coronary artery disease confirmed by uncontrolled arrhythmia, unstable angina pectoris, decompensated congestive heart failure (> New York Heart Association Class II), or myocardial infarction within 6 months prior to cell infusion;
2.Patients with severe liver and kidney dysfunction or consciousness disorder;
3.Patients who received antitumor chemotherapy other than lymphocyte clearance chemotherapy within 14 days prior to CAR T infusion;
4.Patients who received other study drugs within 14 days prior to infusion;
5. Patients treated with radiotherapy or TKI within 2 weeks prior to infusion;
6. Patients with active hepatitis B: HBV DNA>1000IU/mL;
7. HIV antibody, hepatitis C antibody, treponema pallidum antibody positive patients;
8. Sputum smears and patients who test positive for T cells of tuberculosis infection
9.Patients with interstitial lung disease or pneumonia;
10.patients with uncontrolled acute life-threatening bacterial, viral or fungal infection (e.g. positive blood culture ≤72 hours prior to infusion);
11.Patients with central nervous primary tumor or central metastasis solid tumor (patients with stable treatment for more than 4 weeks after brain metastasis or patients with asymptomatic brain metastasis without treatment are excluded from this range), and patients with pericardial metastasis accompanied by large pericardial effusion.
12.Patients with a prior or concurrent second tumor, except in the following cases:
Adequately treated basal cell or squamous cell carcinoma (adequate wound healing required prior to enrollment);
Carcinoma in situ of cervical or breast cancer with no signs of recurrence for at least 3 years prior to study after curative treatment;
The primary malignancy has been completely resected and in complete remission for ≥5 years.
13.Pregnant or lactating women;
14.Patients who have a history of or currently have T-cell tumors;
15. have active neuroautoimmune or inflammatory disorders (e.g. Guillian-Barre syndrome, AMyotrophic lateral sclerosis);
16.Other conditions, such as compliance, that the investigator considers should not be included in this clinical trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhang Zhenfeng, PhD
Phone
+862039195965
Email
zhangzhf@gzhmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luo min, PhD
Organizational Affiliation
Guangzhou Bio-gene Technology Co., Ltd
Official's Role
Study Chair
Facility Information:
Facility Name
Second Affiliated Hospital of Guangzhou Medical University
City
Guangzhou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhang Zhenfeng, MD, PhD
Phone
+862039195966
Email
zhangzhf@gzhmu.edu.cn
12. IPD Sharing Statement
Plan to Share IPD
No
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EGFR/B7H3 CAR-T on Lung Cancer and Triple Negative Breast Cancer
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