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

Phase 1

Completed

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

• Registration Number: NCT02795988
• Lead Sponsor: Imugene Limited

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.

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 Timeline

• Study First Submitted: 2016-06-01
• Study First Submitted QC: 2016-06-09
• Study First Posted: 2016-06-10
• Study Start: 2017-08-30
• Primary Completion: 2024-03-20
• Study Completion: 2024-03-20
• Status Verified: 2025-03
• Results First Submitted: 2025-03-19
• Results First Submitted QC: 2025-04-14
• Last Update Submitted: 2025-04-14
• Results First Posted: 2025-04-16
• Last Update Posted: 2025-04-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2 - IMU 131 plus chemotherapy	Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.	50 μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and Capecitabine.
Phase 2 - Chemotherapy only	Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.	Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and Capecitabine.
Phase 1b	Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.	10, 30, 50μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine
Phase 1b	IMU-131	10, 30, 50μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine
Phase 2 - IMU 131 plus chemotherapy	IMU-131	50 μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and Capecitabine.

Primary Outcome Measures

Name	Time	Method
Phase 1b: Number of Participants With Adverse Events (AEs)	Up to approximately 7 months	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.
Phase 2: Overall Survival (OS)	Up to approximately 30 months	OS was measured from date of randomization to date of death due to any cause.
Phase 2 Extension: Number of Participants With AEs	From date of first dose to date of last dose plus 30 days (Up to 24 months)	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.

Secondary Outcome Measures

Name	Time	Method
Phase 2 and Phase 2 Extension: Disease Control Rate (DCR)	Up to approximately 30 months	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.
Phase 2 and Phase 2 Extension: Objective Response Rate (ORR)	Up to approximately 30 months	ORR was defined as the proportion of participants with a BOR of CR or PR according RECIST 1.1 after randomization/enrollment date.
Phase 2 and Phase 2 Extension: Duration of Response (DOR)	Up to approximately 30 months	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).
Phase 2 and Phase 2 Extension: Percentage Change From Baseline in Tumor Size	Baseline up to approximately 30 months	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).
Phase 2 Extension: OS	Up to 24 months	OS was measured from date of randomization to date of death due to any cause.
Phase 2 and Phase 2 Extension: Progression-Free Survival (PFS)	Up to approximately 30 months	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.
Phase 2 and Phase 2 Extension: Time to Progression (TTP)	Up to approximately 30 months	TTP was measured from randomization to date of earliest PD based on blinded central review according to RECIST 1.1 criteria.

Trial Locations

Locations (21)

ARENSIA Exploratory Medicine LLC; 🇺🇦 Kapitanivka, Ukraine

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

Victoria Hospital; 🇮🇳 Bangalore, India

Deenanath Mangeshkar Hospital and Research Centre; 🇮🇳 Pune, Maharashtra, 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, Republic of

Oncology Institute of Vojvodina; 🇷🇸 Sremska Kamenica, 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, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Division of Medical Oncology, Department of Medicine, Prince of Songkla University, Songklanagarind Hospital; 🇹🇭 Hat Yai, Songkhla Province, Thailand

National Cancer Institute of Thailand; 🇹🇭 Bangkok, Thailand

Division of Oncology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University; 🇹🇭 Chiang Mai, Thailand