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

NCT05311176 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IMU.131.203
• Study Type: interventional
• Target: 7
• Locations: 2 countries
• Sites: 7

Brief Summary

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.

Conditions

Gastric Cancer; Cancer of Stomach; Gastric Adenocarcinoma; Stomach Cancer; Stomach Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Keywords

HER2; Immunotherapy

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• Overall Survival (OS)

  Up to approximately 6 months

• Progression Free Survival (PFS)

  Up to approximately 6 months

• Duration of Response (DoR)

  Up to approximately 6 months

Study Arms (2)

Arm 1: HER-Vaxx in combination with chemotherapy (ramucirumab plus paclitaxel)

EXPERIMENTAL

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; Drug: Ramucirumab plus Paclitaxel

Arm 2: HER-Vaxx in combination with pembrolizumab

EXPERIMENTAL

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; Biological: Pembrolizumab

Interventions

IMU-131 BIOLOGICAL

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.

Also known as: HER-Vaxx

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

Ramucirumab plus Paclitaxel DRUG

Chemotherapy to be administered every 3 weeks (Q3W) starting on Day 1.

Also known as: Standard of Care Chemotherapy

Arm 1: HER-Vaxx in combination with chemotherapy (ramucirumab plus paclitaxel)

Pembrolizumab BIOLOGICAL

Pembrolizumab will be administered every 3 weeks (Q3W) starting on Day 1 until disease progression or treatment discontinuation.

Also known as: Keytruda

Arm 2: HER-Vaxx in combination with pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years with confirmed diagnosis of advanced or metastatic HER2/neu overexpressing gastric or GEJ adenocarcinoma;
• Progressed on or after trastuzumab therapy;
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
• Life expectancy of a minimum of 3 months;
• At least one measurable lesion as defined by RECIST 1.1 criteria and assessed by the local investigator;
• HER2/neu overexpression assessed using post-progression fresh or archival tissue, or post-progression pathology report;
• Adequate left ventricular ejection function at baseline, defined as left ventricular ejection fraction (LVEF) \> 50% by echocardiogram or Multi Gated Acquisition (MUGA) scan;
• Adequate hematologic, liver and renal function;
• 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.

You may not qualify if:

• 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;
• Concurrent active malignancy except for adequately controlled limited basal cell carcinoma of the skin;
• 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;
• 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.
• Previous treatment with trastuzumab-deruxtecan or any other anti-HER2 therapy (except trastuzumab);
• Clinically significant cardiovascular disease, or other diseases that in the Investigator's opinion may influence the patient's tolerance to study treatment;
• Pleural effusion or ascites requiring more than weekly drainage;
• Prior organ transplantation, including allogenic stem-cell transplantation;
• Chronic immunosuppressive therapy within 7 days prior the first dose of study drug;
• Active, known, or suspected autoimmune disease;
• History of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease;
• 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;
• 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;
• Any vaccination within 30 days prior to starting study treatment;
• Pregnant or lactating females;

Sponsors & Collaborators

• Imugene Limited: lead

Study Sites (7)

Southern Medical Day Care Centre

Wollongong, New South Wales, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Kaohsiung Medical University Hospital

Kaohsiung City, Taiwan

Location

National Cheng Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Chang Gung Memorial Hospital, Linkou

Taoyuan, Taiwan

Location

Related Links

• Imugene Limited

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Ramucirumab; Paclitaxel; pembrolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

Some efficacy endpoints could not be analyzed because the study was discontinued after only a small number of participants had been enrolled.

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 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: April 5, 2022
• Study Start: August 17, 2022
• Primary Completion: April 4, 2024
• Study Completion: April 4, 2024
• Last Updated: May 11, 2025
• Results First Posted: May 11, 2025

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

TW (5); AU (2)