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

NCT02795988 | Completed Phase 1 Results DMC

• 1 other identifier: IMU.ACS.001
• Study Type: interventional
• Target: 64
• Locations: 7 countries
• Sites: 22

Brief Summary

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.

Conditions

Gastrointestinal Neoplasms; Adenocarcinoma

Keywords

Secondary

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• Phase 2 and Phase 2 Extension: Progression-Free Survival (PFS)

  Up to approximately 30 months

• Phase 2 and Phase 2 Extension: Time to Progression (TTP)

  Up to approximately 30 months

• Phase 2 and Phase 2 Extension: Disease Control Rate (DCR)

  Up to approximately 30 months

• Phase 2 and Phase 2 Extension: Objective Response Rate (ORR)

  Up to approximately 30 months

• Phase 2 and Phase 2 Extension: Duration of Response (DOR)

  Up to approximately 30 months

Study Arms (3)

Phase 1b

EXPERIMENTAL

10, 30, 50μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine

Biological: IMU-131; Drug: Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.

Phase 2 - IMU 131 plus chemotherapy

EXPERIMENTAL

50 μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and Capecitabine.

Biological: IMU-131; Drug: Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.

Phase 2 - Chemotherapy only

EXPERIMENTAL

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.

Interventions

IMU-131 BIOLOGICAL

IMU-131 vaccine is a P467-CRM197 peptide antigen in PBS buffer and Montanide ISA 51 Sterile adjuvant

Also known as: HER-Vaxx

Phase 1b; Phase 2 - IMU 131 plus chemotherapy

Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine. DRUG

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).

Also known as: Standard of Care Chemotherapy

Phase 1b; Phase 2 - Chemotherapy only; Phase 2 - IMU 131 plus chemotherapy

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Age ≥ 20 years old;
• Life expectancy of at least 12 weeks;
• 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;
• Metastatic gastric or GEJ adenocarcinoma, or locally advanced disease not amenable to surgical resection;
• 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;
• Phase 1b: ECOG performance status 0-1; Phase 2: ECOG performance status 0-2;
• 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;
• Adequate left ventricular ejection function at baseline, defined as LVEF \> 50% by echocardiogram or MUGA scan (Multi Gated Acquisition Scan);
• Adequate hematologic function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL;
• 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;
• Adequate renal function (creatinine ≤ 1.5 x laboratory ULN);
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• 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.

You may not qualify if:

• Previous treatment with trastuzumab or any other HER2/neu targeting antibody or agent;
• 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;
• Prior organ transplant;
• 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;
• 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;
• If on warfarin (Coumadin®) or other vitamin K antagonists;
• Concurrent active malignancy except for adequately controlled limited basal cell carcinoma of the skin;
• Peripheral neuropathy or hearing loss of NCI CTCAE Grade \> 2;
• 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;
• Active infection requiring IV antibiotics;
• 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;
• Pregnant or lactating females;
• Major surgery within 4 weeks prior to study entry. Minor surgery (excluding diagnostic biopsy) within 1 week prior to study entry;
• Has received a live-virus vaccination within 4 weeks of first study vaccination. Seasonal flu vaccines that do not contain live virus are permitted;
• Current or recent (within 4 weeks of first IMU-131 vaccination) treatment with another investigational drug or participation in another investigational study.

Sponsors & Collaborators

• Imugene Limited: lead

Study Sites (22)

ARENSIA Exploratory Medicine LLC

Tbilisi, 0112, Georgia

Location

City Cancer Center

Vijayawada, Andhra Pradesh, 520002, India

Location

North East Cancer Hospital and Research Institute

Guwahati, Assam, 781023, India

Location

Shetty's Hospital

Bengaluru, Karnataka, 560068, India

Location

Curie Manavata Cancer Centre

Nashik, Maharashtra, 422004, India

Location

Deenanath Mangeshkar Hospital and Research Centre

Pune, Maharashtra, 411004, India

Location

Victoria Hospital

Bangalore, 560002, India

Location

MNJ Institute of Oncology and Regional Cancer Centre

Hyderabad, 500004, India

Location

Tata Medical Centre

Kolkata, 700160, India

Location

HCG NCHRI Cancer Centre

Nagpur, 440026, India

Location

Regional Cancer Centre Indira Gandhi Institute of Medical Sciences

Patna, 800014, India

Location

ARENSIA Exploratory Medicine IMSP Institutul Oncologic

Chisinau, 2025, Moldova

Location

Oncology Institute of Vojvodina

Kamenitz, Južnobanatski Okrug, 21204, Serbia

Location

Institute for Oncology and Radiology of Serbia - PPDS

Belgrade, 11000, Serbia

Location

Military Medical Academy

Belgrade, 11000, Serbia

Location

Clinical Hospital Center Bezanijska Kosa

Belgrade, 11070, Serbia

Location

National Cheng-Kung University Hospital

Tainan, 70403, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Division of Medical Oncology, Department of Medicine, Prince of Songkla University, Songklanagarind Hospital

Hat Yai, Changwat Songkhla, 90110, Thailand

Location

National Cancer Institute of Thailand

Bangkok, 10400, Thailand

Location

Division of Oncology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University

Chiang Mai, 50200, Thailand

Location

ARENSIA Exploratory Medicine LLC

Kapitanivka, 8112, Ukraine

Location

Related Publications (2)

• Tobias J, Maglakelidze M, Andric Z, Ryspayeva D, Bulat I, Nikolic I, Petrovic Z, Chawla T, Nagarkar R, Garner-Spitzer E, Zielinski CC, Chong LMO, Nixon B, Ede NJ, Yavrom S, Kundi M, Wiedermann U. Phase II Trial of HER-Vaxx, a B-cell Peptide-Based Vaccine, in HER2-Overexpressing Advanced Gastric Cancer Patients Under Platinum-Based Chemotherapy (HERIZON). Clin Cancer Res. 2024 Sep 13;30(18):4044-4054. doi: 10.1158/1078-0432.CCR-24-0742.

  PMID: 39028916 DERIVED

• 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.

  PMID: 33879458 DERIVED

Related Links

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

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Adenocarcinoma; Neoplasm Metastasis

Interventions

Cisplatin; Fluorouracil; Capecitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Imugene

info@imugene.com

+61 2 9423 0881

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Partially blinded - blinded central review of progression.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2016
• First Posted: June 10, 2016
• Study Start: August 30, 2017
• Primary Completion: March 20, 2024
• Study Completion: March 20, 2024
• Last Updated: April 16, 2025
• Results First Posted: April 16, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

UA (1); IN (10); TW (2); MO (1); TH (3); GE (1); SE (4)