A Study of IMU-131 (HER-Vaxx) in Combination With Chemotherapy or Pembrolizumab in Patients With Metastatic HER2/Neu Over-Expressing Gastric Cancer (nextHERIZON) (nextHERIZON)

nextHERIZON: An Open-Label, Signal Generating, Phase 2 Study of HER-Vaxx in Combination With Chemotherapy or Pembrolizumab in Patients With Metastatic HER2/Neu Over-Expressing Gastric or Gastroesophageal Junction (GEJ) Adenocarcinomas Who Have Previously Received Trastuzumab and Progressed on This Treatment

This is a Phase 2, signal generating, open-label, 2-Arm, non-randomized study, in patients with metastatic HER2/neu over-expressing gastric cancer or gastroesophageal adenocarcinomas.

Study Overview

• Status: Terminated
• Conditions: Stomach Cancer; Gastric Cancer; Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Cancer of Stomach; Stomach Adenocarcinoma
• Intervention / Treatment: Biological: IMU-131; Biological: Pembrolizumab; Drug: Ramucirumab plus Paclitaxel

Detailed Description

It is hypothesized that the introduction of HER-Vaxx after 1L treatment in patients that have progressed under trastuzumab may overcome potential resistance against trastuzumab in combination with chemotherapy and can be continued after chemotherapy is terminated. Based on pre-clinical data HER-Vaxx may also synergize with pembrolizumab and therefore serve as a potentially better tolerated and chemotherapy-free treatment opportunity in metastatic patients that progressed under their previous therapy.

The study is designed to generate safety data and efficacy signals to support further development of HER-Vaxx in ≥2L mGC/GEJ cancer after progression with trastuzumab.

The study includes two treatment arms that will be analyzed independently using a 2-Stage design:

• Arm 1: HER-Vaxx in combination with chemotherapy (ramucirumab plus paclitaxel)
• Arm 2: HER-Vaxx in combination with pembrolizumab.

All patients must have received trastuzumab and progressed after 1L to be eligible for enrolment. Patients who have received an immune checkpoint inhibitor (ICI) previously will exclusively be enrolled in Arm 1 (HER-Vaxx + chemotherapy). Patients who are naïve to ICI treatment will exclusively be enrolled into Arm 2 (HER-Vaxx + pembrolizumab).

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Wollongong, New South Wales, Australia
      • Southern Medical Day Care Centre
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
• Taiwan
  • Kaohsiung City, Taiwan
    • Kaohsiung Medical University Hospital
  • Tainan City, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taoyuan City, Taiwan
    • Chang Gung Memorial Hospital, Linkou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years with confirmed diagnosis of advanced or metastatic HER2/neu overexpressing gastric or GEJ adenocarcinoma;
2. Progressed on or after trastuzumab therapy;
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
4. Life expectancy of a minimum of 3 months;
5. At least one measurable lesion as defined by RECIST 1.1 criteria and assessed by the local investigator;
6. HER2/neu overexpression assessed using post-progression fresh or archival tissue, or post-progression pathology report;
7. Adequate left ventricular ejection function at baseline, defined as left ventricular ejection fraction (LVEF) > 50% by echocardiogram or Multi Gated Acquisition (MUGA) scan;
8. Adequate hematologic, liver and renal function;
9. A female patient of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 120 days after the last dose of assigned treatment.

Exclusion Criteria:

1. Previous malignant disease (other than primary malignancy) within the last 5 years, except basal or squamous cell carcinoma of the skin or cervical carcinoma in situ;
2. Concurrent active malignancy except for adequately controlled limited basal cell carcinoma of the skin;
3. Systemic chemotherapy or major surgery within 28 days before starting study treatment and recovered from all adverse events ≤ Grade 1 or baseline with possible exceptions for neuropathy and endocrine-related AEs;
4. Received prior radiotherapy within 2 weeks of start of study treatment and recovered from all radiation-related toxicities and not require corticosteroids; or history of radiation pneumonitis.
5. Previous treatment with trastuzumab-deruxtecan or any other anti-HER2 therapy (except trastuzumab);
6. Clinically significant cardiovascular disease, or other diseases that in the Investigator's opinion may influence the patient's tolerance to study treatment;
7. Pleural effusion or ascites requiring more than weekly drainage;
8. Prior organ transplantation, including allogenic stem-cell transplantation;
9. Chronic immunosuppressive therapy within 7 days prior the first dose of study drug;
10. Active, known, or suspected autoimmune disease;
11. History of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease;
12. Positivity 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;
13. Current participation or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment;
14. Any vaccination within 30 days prior to starting study treatment;
15. Pregnant or lactating females;
16. Arm 2 only: Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent;
17. Arm 2 only: Has received prior therapy with an ICI or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from treatment due to a grade 3 or higher adverse event.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 2: HER-Vaxx in combination with pembrolizumab; Arm 2 will investigate the combination of HER-Vaxx plus pembrolizumab in patients who are naïve to ICI treatment including patients who have had chemotherapy only treatment after progression on trastuzumab. As the combination treatment has not been investigated, Arm 2 is planned to initiate with a safety run-in phase.	Biological: IMU-131; IMU-131 will be administered intramuscularly into the deltoid region of the arm on Day 1, 15, 29 and 57 and then every 63 days until disease progression or treatment discontinuation.; Other Names: HER-Vaxx; Biological: Pembrolizumab; Pembrolizumab will be administered every 3 weeks (Q3W) starting on Day 1 until disease progression or treatment discontinuation.; Other Names: Keytruda
Experimental: Arm 1: HER-Vaxx in combination with chemotherapy (ramucirumab plus paclitaxel); Patients who have received an immune checkpoint inhibitor (ICI) previously will exclusively be enrolled in Arm 1 treated with HER-Vaxx (IM) in combination with chemotherapy (ramucirumab plus paclitaxel)	Biological: IMU-131; IMU-131 will be administered intramuscularly into the deltoid region of the arm on Day 1, 15, 29 and 57 and then every 63 days until disease progression or treatment discontinuation.; Other Names: HER-Vaxx; Drug: Ramucirumab plus Paclitaxel; Chemotherapy to be administered every 3 weeks (Q3W) starting on Day 1.; Other Names: Standard of Care Chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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.	First dose of study drug up to approximately 1.5 years
Number of Participants With Immune-related Adverse Events (irAEs)	irAEs were monitored throughout the study as per National Comprehensive Cancer Network® (NCCN) guidelines. irAEs were defined as any Grade ≥3 event that did not resolve to Grade 1 (or baseline) within 7 days from the onset of the event, or any Grade ≥3 organ toxicity involving major organ systems that persisted for greater than 72 hours.	First dose of study drug up to approximately 1.5 years
Number of Participants With Objective Response	Objective response was defined as the number of participants achieving a confirmed best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria for Solid Tumors, Version 1.1 (RECIST v1.1).; CR: Disappearance of all target lesions.; PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Up to approximately 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall Survival (OS) was defined as the time from first dose of study drug to death due from any cause.	Up to approximately 6 months
Progression Free Survival (PFS)	PFS was defined as the time from first dose of study drug to first documentation of progressive disease (PD) based on RECIST 1.1, or to death from any cause. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.	Up to approximately 6 months
Duration of Response (DoR)	DoR was measured from earliest CR or PR until first documentation of PD based on RECIST 1.1 or death due to any cause.	Up to approximately 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Outcome: Humoral immunogenicity	Evaluated by P467-specific antibodies and HER2-specific antibodies	From date of enrollment until the date of first documented progression or date of death from any cause, an average of 6 months
Exploratory Outcome: Cellular immunogenicity assessed by multiplex immunoassay	Evaluated by vaccine-specific IL-12p70, IFN-gamma, IL-10, IL-2 and TNF-alpha cytokine levels measured in pg/ml	From date of enrollment until the date of first documented progression or date of death from any cause, an average of 6 months
Exploratory Outcome: Associations between clinical outcome and HER2/neu, PD-L1 expression	Analysis of HER2/neu and PD-L1 expression in pre- and post-treatment tumor biopsies/liquid biopsies (ctDNA/NGS)	From date of enrollment through study completion, an average of 6 months

Collaborators and Investigators

• Sponsor: Imugene Limited

Publications and helpful links

Helpful Links

• Imugene Limited

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2022
• Primary Completion (Actual): April 4, 2024
• Study Completion (Actual): April 4, 2024

Study Registration Dates

• First Submitted: March 8, 2022
• First Submitted That Met QC Criteria: March 27, 2022
• First Posted (Actual): April 5, 2022

Study Record Updates

• Last Update Posted (Actual): May 11, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: HER2; Immunotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplasms, Glandular and Epithelial; Carcinoma; Stomach Neoplasms; Adenocarcinoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ramucirumab; Pembrolizumab; Paclitaxel
• Other Study ID Numbers: IMU.131.203

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No