Her-VAXX / Pevion, Imugene - LARVOL DELTA

A Study of IMU-131 (HER-Vaxx) in Combination With Chemotherapy or Pembrolizumab in Patients With Metastatic HER2/Neu Over-Expressing Gastric Cancer (nextHERIZON) (clinicaltrials.gov) - P2 | N=7 | Terminated | Sponsor: Imugene Limited | Completed ➔ Terminated; Study was discontinued because of slow enrollment and organizational priorities and not because of any findings related to safety or efficacy.

Trial termination • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2

HERIZON: A Study of IMU-131(HER-Vaxx) and Chemotherapy Compared to Chemotherapy Only in Patients With HER2 Positive Advanced Gastric Cancer (clinicaltrials.gov) - P1/2 | N=64 | Completed | Sponsor: Imugene Limited | N=36 ➔ 64

Enrollment change • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • HER-2

Tumor size reduction and overall survival improvement in HER2-overexpressing cancer patients vaccinated with HER-Vaxx, a B-cell peptide-based vaccine, plus standard-of-care chemotherapy (SABCS 2024) - P1/2 | "We have previously identified three peptides representing B cell epitopes on HER2 extracellular domains, comprising trastuzumab's binding site... In gastric/GEJ cancer patients, HER-Vaxx plus standard chemotherapy improves OS, the vaccine-induced immune responses are significantly associated with tumor size reduction, and a favorable safety profile compared to standard-of-care chemotherapy alone is exhibited. This study suggests a possible inclusion of HER-Vaxx as first line treatment modality in HER2-overexpressing cancers."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • FOXP3 • HER-2

A Study of IMU-131 (HER-Vaxx) in Combination with Chemotherapy or Pembrolizumab in Patients with Metastatic HER2/neu Over-Expressing Gastric Cancer (nextHERIZON) (clinicaltrials.gov) - P2 | N=7 | Completed | Sponsor: Imugene Limited | Active, not recruiting ➔ Completed | Trial completion date: Jul 2026 ➔ Apr 2024

Trial completion • Trial completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • IFNG • IL10 • IL2 • PD-L1 • TNFA

HERIZON: A Study of IMU-131(HER-Vaxx) and Chemotherapy Compared to Chemotherapy Only in Patients with HER2 Positive Advanced Gastric Cancer (clinicaltrials.gov) - P1/2 | N=36 | Completed | Sponsor: Imugene Limited | Active, not recruiting ➔ Completed | Trial completion date: Aug 2024 ➔ Mar 2024

Metastases • Trial completion • Trial completion date • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • CD4 • CD8 • HER-2

Final results of the phase II trial of HER-Vaxx, a B-cell peptide-based vaccine plus standard care of chemotherapy in patients with HER2-overexpressing advanced gastric cancer - (HERIZON) (ESMO 2024) - P1/2 | "HER-Vaxx is a B cell peptide-based anti-HER2 vaccine (IMU-131) comprising trastuzumab's binding site... HER-Vaxx plus standard chemotherapy improves the OS benefit and reduces tumor burden, which correlates with vaccine-induced immune response, and exhibits a favorable safety profile compared to standard-of-care chemotherapy alone. HER-Vaxx vaccine is suggested as a first-in-class immunotherapy in combination with standard chemotherapy."

Clinical • Metastases • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • FOXP3 • HER-2

Phase II trial of HER-Vaxx, a B cell peptide-based vaccine, in HER2-overexpressing advanced gastric cancer patients under platinum-based chemotherapy (HERIZON). (PubMed, Clin Cancer Res) - P1/2 | "HER-Vaxx plus standard chemotherapy exhibits an excellent safety profile and improves OS. Furthermore, vaccine-induced immune response was significantly associated with reduced tumor size compared to standard-of-care chemotherapy. The presented vaccination approach may substitute for treatment with trastuzumab, upon unavailability or toxicity, based on further evidence of equivalent treatment efficacy."

Journal • Metastases • P2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FOXP3 • HER-2

Frontline vaccination with the B-cell peptide compound HER-Vaxx (IMU-131), combined with standard-of-care chemotherapy induces high levels of HER2-specific antibodies mediating ADCC and intracellular phosphorylation inhibition resulting in overall survival benefit in patients with HER2+ metastatic or advanced gastric/GEJ adenocarcinoma - Final results from Phase II/HERIZON study (AACR 2024) - P1/2 | "HER-Vaxx is a B cell peptide-based anti-HER2 vaccine (IMU-131) comprising trastuzumab's binding site...Chemotherapy consisted of oxaliplatin plus capecitabine and was started at day 0, repeated every 21 days for a maximum of 6 cycles... The previously shown safety profile of HER-Vaxx, along with the improved clinical and antibody responses in HER2-overexpressing GC patients shown here, validate the proof of concept for a first-in-class B-cell immunotherapy based on HER2 B-cell peptides. Clinical trials evaluating further treatment with HER-Vaxx in HER2+ GC are ongoing."

Clinical • Metastases • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • EGFR • FOXP3

Imugene's oncolytic virotherapy VAXINIA and B cell immunotherapy HER-Vaxx featured at the AACR Annual Meeting 2024 (GlobeNewswire) - "Imugene Limited...is pleased to announce poster presentations featuring its...B cell immunotherapy HER-Vaxx at the American Association for Cancer Research (AACR) Annual Meeting....Highlights include: HER-Vaxx treatment produced robust anti-HER2-IgG and IgG1 antibody response (p<0.001); HER-Vaxx induced HER2-specific antibodies able to mediate antibody-dependent cell cytotoxicity (ADCC) and inhibit intracellular HER2 phosphorylation and correlated with tumour reduction; The HER-Vaxx induced HER2-specific antibodies demonstrate a similar mechanism of action to HERCEPTIN validating B cell immunotherapy as an alternative anti-cancer agent to monoclonal antibodies."

P2 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

HERIZON: A Study of IMU-131(HER-Vaxx) and Chemotherapy Compared to Chemotherapy Only in Patients With HER2 Positive Advanced Gastric Cancer (clinicaltrials.gov) - P1/2 | N=36 | Active, not recruiting | Sponsor: Imugene Limited | Phase classification: P1b/2 ➔ P1/2 | Trial completion date: Feb 2024 ➔ Aug 2024

Metastases • Phase classification • Trial completion date • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • CD4 • CD8 • HER-2

A Study of IMU-131 (HER-Vaxx) in Combination With Chemotherapy or Pembrolizumab in Patients With Metastatic HER2/Neu Over-Expressing Gastric Cancer (nextHERIZON) (clinicaltrials.gov) - P2 | N=7 | Active, not recruiting | Sponsor: Imugene Limited | Recruiting ➔ Active, not recruiting | N=30 ➔ 7

Enrollment change • Enrollment closed • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • IFNG • IL10 • IL2 • PD-L1 • TNFA

Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/neu B-Cell Peptide-Based Vaccine HER-Vaxx and to Prevent Immune Evasion. (PubMed, Int J Mol Sci) - "Her-2/neu-targeting therapy by passive application with trastuzumab is associated with acquired resistance and subsequent metastasis development, which is attributed to the upregulation of tumoral PD-L1 expression and the downregulation of Her-2/neu...The downregulation of Her-2/neu and the upregulation of PD-L1 were observed in a patient's primary tumor at the disease progression time point but not prior to vaccination (Her-2/neu IHC: 3 to 0, FISH: 4.98 to 1.63; PD-L1 CPS: 0% to 5%). Our results further underline the need for combination therapy by targeting PD-L1 to prevent metastasis formation and immune evasion of Her-2/neu-positive and PD-L1-negative tumor cells."

Combination therapy • IO biomarker • Journal • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

HERIZON: A phase II study of HER-Vaxx (IMU-131), a HER2-targeting peptide vaccine plus standard of care chemotherapy in patients with HER2+ advanced stomach cancer - Dose-dependent anti-cancer antibodies correlating with improved clinical outcome (ESMO 2023) - P1b/2 | "Background HER-Vaxx is a B cell peptide-based anti-Her2 vaccine (IMU-131) comprising B cell epitopes located within trastuzumab's binding site...Chemotherapy consisted of oxaliplatin plus capecitabine and was started at day 0, repeated q. 21 days for a maximum of 6 cycles...Moreover, the vaccine-induced IgG antibodies had the capacity to inhibit intracellular phosphorylation of Her2 and exhibited binding to the gastric cancer cell line N87 overexpressing Her2. Conclusions Vaccination with HER-Vaxx in patients with Her2-overexpressing GC at doses of 50μg and 100μg led to an anti-tumour effect that correlated with anti-Her2 IgG antibody levels."

Clinical • Clinical data • Metastases • P2 data • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Prevention of metastasis formation by combination therapy targeting Her2 and PD-L1 in Her2-expressing tumors based on observed efficacious vaccination against Her2-positive tumors (ESMO 2023) - P1b/2 | "We have formulated a Her2 vaccine (HER-Vaxx), comprising B-cell peptide from the trastuzumab binding site, inducing anti-tumor immune responses and immunological memory in pre-clinical and clinical investigations...Conclusions These results strongly suggest an immune evasive tumor cell response with an upregulation of PD-L1 expression in both, the clinical and preclinical settings. A combination therapy targeting both Her2 and PD-L1 in Her2-overexpressing tumors might efficiently prevent metastasis formation and immune evasion."

Combination therapy • IO biomarker • Oncology • HER-2

Imugene to present cancer therapy platforms at prestigious ESMO Congress (Proactiveinvestors) - "Imugene Lt...is gearing up to present two of its innovative therapeutic platforms to some of the world’s most prestigious clinicians, researchers, patient advocates, journalists and industry representatives at the European Society for Medical Oncology (ESMO) Congress. The biotech stock’s B cell immunotherapy, HER-Vaxx, and its CF33 oncolytic virotherapy, CHECKVacc, will take centre stage at the major oncology event in Madrid from October 20 to October 24....Dr Tobias will discuss a Phase 2 study of HER-Vaxx, where Imugene used a HER2-targeting peptide vaccine plus standard of care chemotherapy in patients with HER2+ advanced stomach cancer."

P2 data • Breast Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer

HERIZON: A phase 2 study of HER-Vaxx (IMU-131), a HER2-targeting peptide vaccine plus SOC chemotherapy in patients with HER2+ advanced stomach cancer – correlation of the antibody responses and clinical outcome (ESMO-GI 2023) - P1b/2 | "HER-Vaxx is a B cell peptide-based anti-Her-2/neu vaccine (IMU-131) comprising trastuzumab's binding site...Chemotherapy consisted of oxaliplatin plus capecitabine and was started at day 0, repeated q. 21 days for a maximum of 6 cycles... HER-Vaxx-based vaccination of patients with Her-2 overexpressing GC-induced anti-Her-2-IgG and -IgG1 subclass antibody responses and the magnitude of these antibody responses (total IgG and IgG1) correlated with tumor size reduction. The present data, its previously shown favorable safety profile as well as improved overall survival data induced by HER-Vaxx in Her-2/neu overexpressing GC validate the proof of concept for a first-in-class B-cell immunotherapy based on Her-2/neu peptides."

Clinical • Clinical data • Metastases • P2 data • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • HER-2

Imugene presents new proof of concept data on stomach cancer vaccine at prestigious conference (Proactiveinvestors) - P1b/2 | N=36 | NCT02795988 | Sponsor: Imugene Limited | "Imugene Ltd...has presented new and significant data on HER-Vaxx at the World Congress of Gastrointestinal Cancer in Barcelona....HER-Vaxx treatment resulted in robust anti-HER-2-IgG and IgG1 antibody responses (p<0.001); vaccination with HER-Vaxx in patients with HER-2 overexpressing gastric/gastro-esophageal junction cancer induced anti-HER-2-IgG and IgG1 subclass antibody responses (p<0.001); HER-Vaxx-induced antibodies correlated with tumour reduction (p=0.001); and compared to chemotherapy alone, HER-Vaxx vaccination demonstrated a statistically significant overall survival benefit."

P1/2 data • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of IMU-131 (HER-Vaxx) in Combination With Chemotherapy or Pembrolizumab in Patients With Metastatic HER2/Neu Over-Expressing Gastric Cancer (nextHERIZON) (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Imugene Limited | Trial completion date: Nov 2025 ➔ Jul 2026 | Trial primary completion date: Jul 2023 ➔ Mar 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Immune Modulation • Oncology • Solid Tumor • HER-2

HERIZON: A phase 2 study of HER-Vaxx (IMU-131), a HER2-targeting peptide vaccine, plus standard of care chemotherapy in patients with HER2-overexpressing metastatic or advanced gastric/GEJ adenocarcinoma— Overall survival analysis. (ASCO-GI 2023) - P1b/2 | "Standard chemotherapy consisted of cisplatin + 5FU or capecitabine, or oxaliplatin + capecitabine... These data demonstrate that in patients with HER2 over-expressing gastric/GEJ cancer active HER2 immunization with HER-Vaxx is safe and provides relevant clinical benefit over standard of care chemotherapy. Clinical trial information: NCT02795988."

Clinical • Metastases • P2 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • HER-2

nextHERIZON: A phase 2 study of HER-Vaxx, a HER2-targeting peptide vaccine, in combination with chemotherapy or pembrolizumab in patients with HER2 metastatic or advanced gastric/gastroesophageal adenocarcinoma that progressed on or after trastuzumab treatment. (ASCO-GI 2023) - P2 | "Ramucirumab plus paclitaxel is an approved second-line treatment for patients with GC or GEA who have failed first-line treatment chemotherapy or trastuzumab (TRA) (Wilke, 2014)...Key exclusion criteria include previous treatment with trastuzumab-deruxtecan or any other anti-HER2 therapy other than trastuzumab...This study is currently enrolling patients in Australia and US (Q1 2023). Clinical trial information: NCT05311176."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PD-L2

HERIZON overall survival results: A study of IMU-131, a HER2 targeting peptide vaccine, plus standard of care chemotherapy in patients with HER2 overexpressing metastatic or advanced gastric/GEJ cancer (ESMO Asia 2022) - P1b/2 | "Chemotherapy consisted of cisplatin + 5FU or capecitabine, or oxaliplatin + capecitabine...Additional data on response and biomarker evaluation is pending. Conclusions These results demonstrate that active immunization with the B-lymphocyte stimulating HER2 vaccine, IMU-131 (HER-Vaxx), may provide treatment benefits consistent with traditional monoclonal antibodies with a corresponding adaptive immune response without added toxicity."

Clinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • HER-2

HERIZON: A Study of IMU-131(HER-Vaxx) and Chemotherapy Compared to Chemotherapy Only in Patients With HER2 Positive Advanced Gastric Cancer (clinicaltrials.gov) - P1b/2 | N=36 | Active, not recruiting | Sponsor: Imugene Limited | Trial completion date: Feb 2022 ➔ Feb 2024 | Trial primary completion date: Jan 2022 ➔ Jan 2024

Metastases • Trial completion date • Trial primary completion date • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • HER-2

"Q2 continues: HER-Vaxx generates immune response with memory cells unlike T" (@tanujucms)

Imugene HER-Vaxx and CF33 platforms feature at ASCO Gastrointestinal Cancers Symposium (Proactiveinvestors) - "Imugene Ltd...has made several presentations, including an oral abstract and several poster sessions, on the company’s HER-Vaxx and CF33 technologies at the ASCO Gastrointestinal Cancers Symposium currently being held in San Francisco, US....Imugene’s chief medical officer Dr Giovanni Selvaggi presented this poster as part of a Trials in Progress Poster Session, outlining an introduction to HER-Vaxx and its clinical programme, the study design, objectives and key eligibility criteria."

Trial status • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

HER-Vaxx Improves Survival in HER2+ Advanced Gastric/GEJ Cancer (Cancer Therapy Advisor) - P1b/2 | N=36 | HERIZON (NCT02795988) | Sponsor: Imugene Limited | "Combining HER-Vaxx with standard chemotherapy improves survival in patients with HER2-overexpressing, advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to results from the HERIZON trial....The median OS was 14.0 months in the HER-Vaxx arm and 8.3 months in the chemotherapy-alone arm (hazard ratio, 0.558; 2-sided 80% CI, 0.349-0.895; P =.054). The median progression-free survival was 6.93 months in the HER-Vaxx arm and 6.01 months in the chemotherapy-alone arm. There were 7 responses in each arm. The only complete response occurred in the HER-Vaxx arm."

P2 data • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor