A Study of IMU-131(HER-Vaxx) and Chemotherapy Compared to Chemotherapy Only in Patients With HER2 Positive Advanced Gastric Cancer

A Phase 1b/2 Open-Label Study With Randomization in Phase 2 of IMU-131 HER2/Neu Peptide Vaccine Plus Standard of Care Chemotherapy in Patients With HER2/Neu Overexpressing Metastatic or Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction

The Phase 1b study is an open-label, multicenter dose escalation study designed to assess the safety, tolerability, immunogenicity and recommended phase 2 dose (RP2D) of IMU-131. The RP2D will be evaluated in the dose expansion Phase 2 study. The Phase 2 study is a randomized, open label comparison of IMU-131 plus standard of care chemotherapy versus standard of care chemotherapy alone.

Study Overview

• Status: Completed
• Conditions: Adenocarcinoma; Gastrointestinal Neoplasms
• Intervention / Treatment: Biological: IMU-131; Drug: Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.

Detailed Description

IMU-131 is a single peptide structure composed of 3 individual B-cell epitope peptide sequences selected from HER2/neu structure. Polyclonal antibodies against IMU-131 peptides bind three separate regions of the HER2 receptor and also to the dimerization loop of the HER2 receptor, preventing dimerization, which in turn inhibits intracellular signaling. This blockade of the HER2 signaling pathways is thought to be substantially greater than that with trastuzumab alone. Safety and immunogenicity of the 3 peptides have been shown in Phase 1a testing of an earlier formulation of IMU-131. The shelf stability of the Phase 1a vaccine was not optimal and hence the formulation was adjusted for IMU-131. The three B-cell epitope peptides (P4, P6 and P7) were combined in a specific order resulting in a single fusion peptide of 49 amino acids in length (P467). This new formulation of IMU-131 has extended stability and improved immunogenicity compared to the formulation used previously. The new vaccine IMU-131 produces a stronger and more rapid polyclonal antibody response and is efficient to manufacture compared with previous formulations. Based on these three known epitopes (P4, P6 and P7), the investigators developed a single peptide antigen (P467), which allows simplification of the manufacturing process.

It is hypothesized that administration of IMU-131 in addition to chemotherapy will prolong survival and may delay tumor progression and/or reduce tumor burden in patients with HER2/neu overexpressing gastric or gastroesophageal junction (GEJ) adenocarcinoma (otherwise known as Advanced Cancer of the Stomach (ASC)).

The Phase 1b study aims to determine the safety and tolerability of IMU-131 and identify the Recommended Phase 2 Dose (RP2D) of IMU-131 in combination with chemotherapy in HER2/neu overexpressing ACS to carry into the Phase 2 dose expansion study. The Phase 2 component will be submitted as an amendment and will be initiated following completion of Phase 1b. Phase 2 will be designed to further characterize the safety and to explore clinical activity of IMU-131 in combination with chemotherapy in HER2/neu overexpressing ACS.The Phase 2 study is a randomized, open label comparison of IMU-131 plus standard of care chemotherapy versus standard of care chemotherapy alone.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Georgia
  • Tbilisi, Georgia, 0112
    • ARENSIA Exploratory Medicine LLC
• India
  • Bangalore, India, 560002
    • Victoria Hospital
  • Hyderabad, India, 500004
    • MNJ Institute of Oncology and Regional Cancer Centre
  • Kolkata, India, 700160
    • TATA Medical Centre
  • Nagpur, India, 440026
    • HCG NCHRI Cancer Centre
  • Patna, India, 800014
    • Regional Cancer Centre Indira Gandhi Institute of Medical Sciences
  • Andhra Pradesh
    • Vijayawada, Andhra Pradesh, India, 520002
      • City Cancer Center
  • Assam
    • Guwahati, Assam, India, 781023
      • North East Cancer Hospital and Research Institute
  • Karnataka
    • Bengaluru, Karnataka, India, 560068
      • Shetty's Hospital
  • Maharashtra
    • Nashik, Maharashtra, India, 422004
      • Curie Manavata Cancer Centre
    • Pune, Maharashtra, India, 411004
      • Deenanath Mangeshkar Hospital and Research Centre
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, 2025
    • ARENSIA Exploratory Medicine IMSP Institutul Oncologic
• Serbia
  • Belgrade, Serbia, 11000
    • Military Medical Academy
  • Belgrade, Serbia, 11000
    • Institute for Oncology and Radiology of Serbia - PPDS
  • Belgrade, Serbia, 11070
    • Clinical Hospital Center Bezanijska Kosa
  • Južnobanatski Okrug
    • Sremska Kamenica, Južnobanatski Okrug, Serbia, 21204
      • Oncology Institute of Vojvodina
• Taiwan
  • Tainan, Taiwan, 70403
    • National Cheng-Kung University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
• Thailand
  • Bangkok, Thailand, 10400
    • National Cancer Institute of Thailand
  • Chiang Mai, Thailand, 50200
    • Division of Oncology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University
  • Songkhla Province
    • Hat Yai, Songkhla Province, Thailand, 90110
      • Division of Medical Oncology, Department of Medicine, Prince of Songkla University, Songklanagarind Hospital
• Ukraine
  • Kapitanivka, Ukraine, 8112
    • ARENSIA Exploratory Medicine LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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. Phase 1b: No prior chemotherapy or radiotherapy for advanced gastric or GEJ cancer within 6 months prior to Day 0; Phase 2: No prior chemotherapy or radiotherapy for advanced gastric or GEJ cancer within 3 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. Phase 1b: ECOG performance status 0-1; Phase 2: ECOG performance status 0-2;
8. At least one measurable lesion as defined by RECIST 1.1 criteria. Patients with non-measurable 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/L, platelet count ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL;
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:

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. Phase 1b: Patient not considered a candidate for 5-FU, capecitabine, or cisplatin chemotherapy; Phase 2: Patient not considered a candidate for 5-FU, capecitabine, cisplatin or oxaliplatin 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.
16. Phase 2: Patients with a known diphtheria toxoid hypersensitivity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b; 10, 30, 50μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine	Biological: IMU-131; IMU-131 vaccine is a P467-CRM197 peptide antigen in PBS buffer and Montanide ISA 51 Sterile adjuvant; Other Names: HER-Vaxx; Drug: Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.; Chemotherapy will consist of: cisplatin by intravenous administration at 80 mg/m2 on the first day of each cycle and either 5-FU, 4000 mg/m2 CIV (administered as 1000 mg/m2/day as continuous infusion for 96 hours on days 1 to 4 of each cycle) or capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle), or (in Phase 2 only) oxaliplatin, by intravenous administration at 130 mg/m2 on Day 1 of each cycle and capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle).; Other Names: Standard of Care Chemotherapy
Experimental: Phase 2 - IMU 131 plus chemotherapy; 50 μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and Capecitabine.	Biological: IMU-131; IMU-131 vaccine is a P467-CRM197 peptide antigen in PBS buffer and Montanide ISA 51 Sterile adjuvant; Other Names: HER-Vaxx; Drug: Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.; Chemotherapy will consist of: cisplatin by intravenous administration at 80 mg/m2 on the first day of each cycle and either 5-FU, 4000 mg/m2 CIV (administered as 1000 mg/m2/day as continuous infusion for 96 hours on days 1 to 4 of each cycle) or capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle), or (in Phase 2 only) oxaliplatin, by intravenous administration at 130 mg/m2 on Day 1 of each cycle and capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle).; Other Names: Standard of Care Chemotherapy
Experimental: Phase 2 - Chemotherapy only; Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and Capecitabine.	Drug: Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.; Chemotherapy will consist of: cisplatin by intravenous administration at 80 mg/m2 on the first day of each cycle and either 5-FU, 4000 mg/m2 CIV (administered as 1000 mg/m2/day as continuous infusion for 96 hours on days 1 to 4 of each cycle) or capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle), or (in Phase 2 only) oxaliplatin, by intravenous administration at 130 mg/m2 on Day 1 of each cycle and capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle).; Other Names: Standard of Care Chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: Number of Participants With Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in the Reported AE section.	Up to approximately 7 months
Phase 2: Overall Survival (OS)	OS was measured from date of randomization to date of death due to any cause.	Up to approximately 30 months
Phase 2 Extension: Number of Participants With AEs	An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in the Reported AE section.	From date of first dose to date of last dose plus 30 days (Up to 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2 and Phase 2 Extension: Progression-Free Survival (PFS)	PFS was measured from randomization to date of earliest progressive disease (PD) based on blinded central review according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, or to date of death from any cause.	Up to approximately 30 months
Phase 2 and Phase 2 Extension: Time to Progression (TTP)	TTP was measured from randomization to date of earliest PD based on blinded central review according to RECIST 1.1 criteria.	Up to approximately 30 months
Phase 2 and Phase 2 Extension: Disease Control Rate (DCR)	DCR was defined as the percentage of participants with a Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), or stable disease according to RECIST 1.1 after randomization/enrollment date.	Up to approximately 30 months
Phase 2 and Phase 2 Extension: Objective Response Rate (ORR)	ORR was defined as the proportion of participants with a BOR of CR or PR according RECIST 1.1 after randomization/enrollment date.	Up to approximately 30 months
Phase 2 and Phase 2 Extension: Duration of Response (DOR)	DOR was defined as the time from the earliest date when a tumor response of CR or PR was observed until the date of first occurrence of disease progression which assessed by the blinded central reviewer or death (due to any reason).	Up to approximately 30 months
Phase 2 and Phase 2 Extension: Percentage Change From Baseline in Tumor Size	Change in tumor size (CTS) was measured as the sum of diameters based on blinded central review according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1).	Baseline up to approximately 30 months
Phase 2 Extension: OS	OS was measured from date of randomization to date of death due to any cause.	Up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Outcome (Phase 1b): Humoral immunogenicity evaluated by P467-specific antibodies (IgG) and Her-2- specific antibodies (IgG)	Antibodies analysed in serum samples taken across study visits	Day 0 to Progression (approx. 7.5 months)
Exploratory Outcome (Phase 1b): Cellular immunogenicity evaluated by vaccine-specific cytokine levels as well as analysis of regulatory and effector T and B cells	Vaccine-specific cytokine levels and regulatory and effector T and B cells analysed in whole blood samples	Day 0 to Progression (approx. 7.5 months)
Exploratory Outcome (Phase 1b): Radiographic data measured by RECIST 1.1 criteria	Radiographic data will be analyzed descriptively to explore the Response Rate (RR)	Day 0 to Progression (approx. 7.5 months)
Exploratory Outcome (Phase 2): Measurement of Serum Prediction Marker of Tumor Progression	To measure the changes from baseline of serum prediction marker of tumor progression in ng/ml.	Day 0 to Progression (approx. 7.5 months)
Exploratory Outcome (Phase 2): Measurement of immunological and biochemical markers	To measure the changes from baseline of intra-tumor T cells and biochemical markers including CD4+, CD8+ T cells & Treg cells in ng/ml.	Day 0 to Progression (approx. 7.5 months)

Collaborators and Investigators

• Sponsor: Imugene Limited

Publications and helpful links

General Publications

• Wiedermann U, Garner-Spitzer E, Chao Y, Maglakelidze M, Bulat I, Dechaphunkul A, Arpornwirat W, Charoentum C, Yen CJ, Yau TC, Tanasanvimon S, Maneechavakajorn J, Sookprasert A, Bai LY, Chou WC, Ungtrakul T, Drinic M, Tobias J, Zielinski CC, Chong L, Ede NJ, Marino MT, Good AJ. Clinical and Immunologic Responses to a B-Cell Epitope Vaccine in Patients with HER2/neu-Overexpressing Advanced Gastric Cancer-Results from Phase Ib Trial IMU.ACS.001. Clin Cancer Res. 2021 Jul 1;27(13):3649-3660. doi: 10.1158/1078-0432.CCR-20-3742. Epub 2021 Apr 20.

Helpful Links

• Imugene (ASX: IMU) is a publicly-listed biotechnology company.

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2017
• Primary Completion (Actual): March 20, 2024
• Study Completion (Actual): March 20, 2024

Study Registration Dates

• First Submitted: June 1, 2016
• First Submitted That Met QC Criteria: June 9, 2016
• First Posted (Estimated): June 10, 2016

Study Record Updates

• Last Update Posted (Actual): April 16, 2025
• Last Update Submitted That Met QC Criteria: April 14, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Secondary
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms, Glandular and Epithelial; Carcinoma; Gastrointestinal Neoplasms; Adenocarcinoma; Digestive System Neoplasms; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Capecitabine; Oxaliplatin; Fluorouracil
• Other Study ID Numbers: IMU.ACS.001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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