Clinical Trials List
Protocol NumberIMU.ACS.001
2016-06-03 - 2021-02-01
Others
Terminated3
Study ended1
ICD-10C16.0
Malignant neoplasm of cardia
ICD-10C16
Malignant neoplasm of stomach
ICD-9151.0
Malignant neoplasm of cardia of stomach
A Phase 1b/2 Open-label Study of IMU-131 HER2/neu Peptide Vaccine Plus Cisplatin and either 5-Fluorouracil or Capecitabine Chemotherapy in Patients with HER2/neu Overexpressing Metastatic or Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction
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Sponsor
Imugene Limited
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Rheun-Chuan Lee Division of Hematology & Oncology
- Ming-Huang Chen Division of Hematology & Oncology
- Chung-Pin Li Division of Hematology & Oncology
- Yi-Ping Hung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
4 Stop recruiting
Audit
None
Co-Principal Investigator
- Yan-Shen Shan Division of General Internal Medicine
- 劉奕廷 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
Audit
None
Linkou Chang Gung Medical Foundation
Taiwan National PI
周文其
Co-Principal Investigator
- Tsai-Sheng Yang Division of Hematology & Oncology
- Yung-Chia Kao Division of Hematology & Oncology
- Hung-Chih Hsu Division of Hematology & Oncology
- Po-Jung Su Division of Hematology & Oncology
- Chia-Hsun Hsieh Division of Hematology & Oncology
- Jen-Shi Chen Division of Hematology & Oncology
- Ming-Mo Hou Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Chang-Fang Chiu Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Study ended
Condition/Disease
Adenocarcinoma of the Stomach
Objectives
• To evaluate the safety and tolerability of IMU-131 administered intramuscularly (IM) and initiated 14 days (+/- 1 day) prior to cisplatin, intravenous (IV) and either 5-FU, IV or capecitabine, oral (hereafter referred to as Chemotherapy) in patients with
HER2/neu overexpressing ACS;
• To identify the Recommended Phase 2 Dose of IMU-131, administered IM and initiated 14 days (+/- 1 day) prior to Chemotherapy in patients with HER2/neu overexpressing ACS
for evaluation in Phase 2.
Exploratory objectives of Phase 1b study:
• Humoral and tumoral immunogenicity data will be used to further explore the mechanism of action for anti-tumor effects of IMU131;
• Radiographic data will be used for an exploratory determination of Response Rate.
Test Drug
IMU-131
Active Ingredient
P467-CRM197
Dosage Form
IM
Dosage
10
30
50
30
50
Endpoints
Phase 1b study endpoints:
• The safety and tolerability of IMU-131 will be evaluated by adverse events (AEs) and laboratory measurements. AEs and laboratory abnormalities will be graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.03;
• The recommended phase 2 dose will be evaluated by safety/tolerability and immunogenicity data for IMU-131 (P467-specific antibodies (IgG) and Her-2- specific antibodies (IgG) titers).
Phase 1b study exploratory endpoints:
• Humoral and cellular immunogenicity data will include P467- specific antibodies (IgG) and Her-2- specific antibodies (IgG) in serum samples and vaccine-specific cytokine levels as well as analysis of regulatory and effector T and B cells taken across study visits. As prediction markers of tumor progression initial evaluation (prior first vaccination) of intratumoral T cells and regulatory cells in tumor biopsies will be performed, when these tests are available at the hospital pathology laboratory.
• Radiographic data will be analyzed descriptively to explore Response Rate and provide information for sample size calculation for the Phase 2 study.
• The safety and tolerability of IMU-131 will be evaluated by adverse events (AEs) and laboratory measurements. AEs and laboratory abnormalities will be graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.03;
• The recommended phase 2 dose will be evaluated by safety/tolerability and immunogenicity data for IMU-131 (P467-specific antibodies (IgG) and Her-2- specific antibodies (IgG) titers).
Phase 1b study exploratory endpoints:
• Humoral and cellular immunogenicity data will include P467- specific antibodies (IgG) and Her-2- specific antibodies (IgG) in serum samples and vaccine-specific cytokine levels as well as analysis of regulatory and effector T and B cells taken across study visits. As prediction markers of tumor progression initial evaluation (prior first vaccination) of intratumoral T cells and regulatory cells in tumor biopsies will be performed, when these tests are available at the hospital pathology laboratory.
• Radiographic data will be analyzed descriptively to explore Response Rate and provide information for sample size calculation for the Phase 2 study.
Inclution Criteria
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the
study:
1. Patient has been informed of the investigational nature of this study and has given
written informed consent in accordance with institutional, local, and national
guidelines;
2. Age ≥ 20 years old;
3. Life expectancy of at least 12 weeks;
4. No prior chemotherapy or radiotherapy for advanced gastric or GEJ cancer within 6
months prior to Day 0;
5. Metastatic gastric or GEJ adenocarcinoma, or locally advanced disease not amenable to surgical resection;
6. HER2/neu overexpression (3+ by immunohistochemistry (IHC) or if IHC 2+ confirmed by fluorescent in situ hybridization [FISH] or chromogenic in situ hybridization [CISH]). Patients with IHC 2+ expression without confirmation of overexpression by fluorescent in situ hybridization [FISH] or chromogenic in situ hybridization [CISH]) may be included in Phase 1b with agreement of Imugene Limited;
7. ECOG performance status 0–1;
8. At least one measurable lesion as defined by RECIST 1.1 criteria. Patients with onmeasurable lesions may be included in Phase1b with agreement of Imugene Limited.;
9. Adequate left ventricular ejection function at baseline, defined as LVEF > 50% by
echocardiogram or MUGA scan (Multi Gated Acquisition Scan);
10. Adequate hematologic function: absolute neutrophil count (ANC) ≥ 1.5 x 109 platelet count ≥ 100 x 109 and hemoglobin ≥ 9 g/
11. Adequate liver function evidenced by bilirubin ≤ 1.5 x laboratory upper limit of
normal [ULN], and ALT and AST ≤ 3 x laboratory ULN if no liver involvement or ALT and AST ≤ 5 times laboratory ULN with liver involvement;
12. Adequate renal function (creatinine ≤ 1.5 x laboratory ULN);
13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other study procedures.
14. Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment (see section 4.3 for details). A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
study:
1. Patient has been informed of the investigational nature of this study and has given
written informed consent in accordance with institutional, local, and national
guidelines;
2. Age ≥ 20 years old;
3. Life expectancy of at least 12 weeks;
4. No prior chemotherapy or radiotherapy for advanced gastric or GEJ cancer within 6
months prior to Day 0;
5. Metastatic gastric or GEJ adenocarcinoma, or locally advanced disease not amenable to surgical resection;
6. HER2/neu overexpression (3+ by immunohistochemistry (IHC) or if IHC 2+ confirmed by fluorescent in situ hybridization [FISH] or chromogenic in situ hybridization [CISH]). Patients with IHC 2+ expression without confirmation of overexpression by fluorescent in situ hybridization [FISH] or chromogenic in situ hybridization [CISH]) may be included in Phase 1b with agreement of Imugene Limited;
7. ECOG performance status 0–1;
8. At least one measurable lesion as defined by RECIST 1.1 criteria. Patients with onmeasurable lesions may be included in Phase1b with agreement of Imugene Limited.;
9. Adequate left ventricular ejection function at baseline, defined as LVEF > 50% by
echocardiogram or MUGA scan (Multi Gated Acquisition Scan);
10. Adequate hematologic function: absolute neutrophil count (ANC) ≥ 1.5 x 109 platelet count ≥ 100 x 109 and hemoglobin ≥ 9 g/
11. Adequate liver function evidenced by bilirubin ≤ 1.5 x laboratory upper limit of
normal [ULN], and ALT and AST ≤ 3 x laboratory ULN if no liver involvement or ALT and AST ≤ 5 times laboratory ULN with liver involvement;
12. Adequate renal function (creatinine ≤ 1.5 x laboratory ULN);
13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other study procedures.
14. Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment (see section 4.3 for details). A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
Exclusion Criteria
Patients presenting with any of the following will not be included in the study:
1. Previous treatment with trastuzumab or any other HER2/neu targeting antibody or
agent;
2. Continuous systemic treatment with either corticosteroids (>10 mg daily prednisone
equivalents) or other immunosuppressive medications within 4 weeks prior to first dose of study treatment. Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalents are permitted in the absence of active auto-immune disease;
3. Prior organ transplant;
4. Patient not considered a candidate for 5-FU, capecitabine, or cisplatin chemotherapy;
5. History of documented congestive heart failure; angina pectoris requiring antianginal
medication; evidence of transmural infarction on ECG; poorly controlled hypertension; clinically significant valvular heart disease; high risk uncontrolled arrhythmias; or New York Heart Association (NYHA) class II heart disease;
6. If on warfarin (Coumadin®) or other vitamin K antagonists;
7. Concurrent active malignancy except for adequately controlled limited basal cell carcinoma of the skin;
8. Peripheral neuropathy or hearing loss of NCI CTCAE Grade > 2;
9. History of uncontrolled seizures, central nervous disorders or psychiatric disability
judged by the investigator to be clinically significant and precluding informed consent, participation in the study, or adversely affecting compliance to study drugs;
10. Active infection requiring IV antibiotics;
11. Positive for human immunodeficiency virus (HIV) (HIV 1/2 antibodies) or active hepatitis B (HBsAg reactive) or active hepatitis C (HCV ribonucleic acid [RNA] qualitative) infection;
12. Pregnant or lactating females;
13. Major surgery within 4 weeks prior to study entry. Minor surgery (excluding diagnostic biopsy) within 1 week prior to study entry;
14. Has received a live-virus vaccination within 4 weeks of first study vaccination.
Seasonal flu vaccines that do not contain live virus are permitted;
15. Current or recent (within 4 weeks of first IMU-131 vaccination) treatment with another investigational drug or participation in another investigational study.
1. Previous treatment with trastuzumab or any other HER2/neu targeting antibody or
agent;
2. Continuous systemic treatment with either corticosteroids (>10 mg daily prednisone
equivalents) or other immunosuppressive medications within 4 weeks prior to first dose of study treatment. Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalents are permitted in the absence of active auto-immune disease;
3. Prior organ transplant;
4. Patient not considered a candidate for 5-FU, capecitabine, or cisplatin chemotherapy;
5. History of documented congestive heart failure; angina pectoris requiring antianginal
medication; evidence of transmural infarction on ECG; poorly controlled hypertension; clinically significant valvular heart disease; high risk uncontrolled arrhythmias; or New York Heart Association (NYHA) class II heart disease;
6. If on warfarin (Coumadin®) or other vitamin K antagonists;
7. Concurrent active malignancy except for adequately controlled limited basal cell carcinoma of the skin;
8. Peripheral neuropathy or hearing loss of NCI CTCAE Grade > 2;
9. History of uncontrolled seizures, central nervous disorders or psychiatric disability
judged by the investigator to be clinically significant and precluding informed consent, participation in the study, or adversely affecting compliance to study drugs;
10. Active infection requiring IV antibiotics;
11. Positive for human immunodeficiency virus (HIV) (HIV 1/2 antibodies) or active hepatitis B (HBsAg reactive) or active hepatitis C (HCV ribonucleic acid [RNA] qualitative) infection;
12. Pregnant or lactating females;
13. Major surgery within 4 weeks prior to study entry. Minor surgery (excluding diagnostic biopsy) within 1 week prior to study entry;
14. Has received a live-virus vaccination within 4 weeks of first study vaccination.
Seasonal flu vaccines that do not contain live virus are permitted;
15. Current or recent (within 4 weeks of first IMU-131 vaccination) treatment with another investigational drug or participation in another investigational study.
The Estimated Number of Participants
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Taiwan
9 participants
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Global
68 participants
