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

NCT ID: NCT02795988

Last Updated: 2025-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-30
• Study Completion Date: 2024-03-20

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Phase 1b

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

Group Type: EXPERIMENTAL

IMU-131

Intervention Type: BIOLOGICAL

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

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

Intervention Type: 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).

Phase 2 - IMU 131 plus chemotherapy

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

Group Type: EXPERIMENTAL

IMU-131

Intervention Type: BIOLOGICAL

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

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

Intervention Type: 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).

Phase 2 - Chemotherapy only

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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).

Interventions

IMU-131

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

Intervention Type: BIOLOGICAL

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).

Intervention Type: DRUG

Other Intervention Names

HER-Vaxx; Standard of Care Chemotherapy

Eligibility Criteria

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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Imugene Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

ARENSIA Exploratory Medicine LLC

Tbilisi, , Georgia

City Cancer Center

Vijayawada, Andhra Pradesh, India

North East Cancer Hospital and Research Institute

Guwahati, Assam, India

Shetty's Hospital

Bengaluru, Karnataka, India

Curie Manavata Cancer Centre

Nashik, Maharashtra, India

Deenanath Mangeshkar Hospital and Research Centre

Pune, Maharashtra, India

Victoria Hospital

Bangalore, , India

MNJ Institute of Oncology and Regional Cancer Centre

Hyderabad, , India

Tata Medical Centre

Kolkata, , India

HCG NCHRI Cancer Centre

Nagpur, , India

Regional Cancer Centre Indira Gandhi Institute of Medical Sciences

Patna, , India

ARENSIA Exploratory Medicine IMSP Institutul Oncologic

Chisinau, , Moldova

Oncology Institute of Vojvodina

Kamenitz, Južnobanatski Okrug, Serbia

Institute for Oncology and Radiology of Serbia - PPDS

Belgrade, , Serbia

Military Medical Academy

Belgrade, , Serbia

Clinical Hospital Center Bezanijska Kosa

Belgrade, , Serbia

National Cheng-Kung University Hospital

Tainan City, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

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

Hat Yai, Changwat Songkhla, Thailand

National Cancer Institute of Thailand

Bangkok, , Thailand

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

Chiang Mai, , Thailand

ARENSIA Exploratory Medicine LLC

Kapitanivka, , Ukraine

Countries

Georgia; India; Moldova; Serbia; Taiwan; Thailand; Ukraine

References

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.

Reference Type: DERIVED

PMID: 39028916 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33879458 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.imugene.com/

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

Other Identifiers

IMU.ACS.001

Identifier Type: -

Identifier Source: org_study_id