Her-VAXX

P2, N=7, Completed, Imugene Limited | Active, not recruiting --> Completed | Trial completion date: Jul 2026 --> Apr 2024

P1/2, N=36, Completed, Imugene Limited | Active, not recruiting --> Completed | Trial completion date: Aug 2024 --> Mar 2024

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.

P1/2, N=36, Active, not recruiting, Imugene Limited | Phase classification: P1b/2 --> P1/2 | Trial completion date: Feb 2024 --> Aug 2024

P2, N=7, Active, not recruiting, Imugene Limited | Recruiting --> Active, not recruiting | N=30 --> 7

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.

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.

P2, N=30, Recruiting, Imugene Limited | Trial completion date: Nov 2025 --> Jul 2026 | Trial primary completion date: Jul 2023 --> Mar 2024

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.

P1b/2, N=36, Active, not recruiting, Imugene Limited | Trial completion date: Feb 2022 --> Feb 2024 | Trial primary completion date: Jan 2022 --> Jan 2024

Cancer vaccines have the ability to stimulate the native immune system and in particular engineered B cell epitopes can elicit high affinity polyclonal antibodies with similar efficacy to Her-2 monoclonal antibodies such as trastuzumab (Roche)...These studies were performed to support clinical development of HER-Vaxx. Results from the GLP toxicology study in rodents showed that the vaccine did not produce any observable adverse effects suggesting that the doses proposed for the clinical trial should be well tolerated in patients.

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.

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.

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.

P2, N=30, Recruiting, Imugene Limited | Not yet recruiting --> Recruiting | Initiation date: May 2022 --> Aug 2022

Furthermore, the loss of Her-2/neu expression suggests a combination therapy involving an anti-PD-L1 immune checkpoint inhibitor or an active immunization with a mimotope from PD-L1. Such combination therapy to alternately target Her-2/neu and PD-L1 might be adapted to the stage and progression phase of the disease and result in the remission of the metastases.

P2, N=30, Not yet recruiting, Imugene Limited

In pre-clinical and clinical settings, active immunization with a Her-2/neu vaccine (HerVaxx), comprising B-cell peptide from Trastuzumab binding site, has been shown to reduce primary tumor growth via induction of polyclonal anti-tumor immune responses and immunological memory. Here, we tested the combination of HerVaxx and the recently identified B-cell epitope/mimotope of Pertuzumab, i.e. a multi-peptide B-cell vaccine, for preventing Her-2/neu lung metastases formation in a mouse model...Moreover, combination therapy targeting PD-L1 may result in total remission of metastases. Such a therapy may be used clinically to alternately target Her-2/neu and PD-L1 in metastatic breast cancer.

Our data might potentially result in a multi-peptide B cell Her-2/neu vaccine serving as a secondary intervention in adjuvant settings to prevent tumor recurrence and spread. Moreover, our suggest a combination therapy involving an anti-PD-L1 immune checkpoint inhibitor or potentially active immunization with a mimotope from PD-L1 to result in the remission of the metastases. Such a combination therapy to alternately target Her-2/neu and PD-L1 could be adapted to the stage and progression phase of the disease.

Conclusions This analysis demonstrated that HER-Vaxx-induced antibodies have similar functionality as trastuzumab, targeting HER2/neu epidermal growth factor...The study has completed enrollment and the final data are expected in late 2021. HER-Vaxx could represent an important cost-effective treatment option for HER2 overexpressing malignancies and may show synergy with other immunotherapy agents, such as checkpoint inhibitors, in subsequent studies.

P1b/2, N=36, Active, not recruiting, Imugene Limited | Recruiting --> Active, not recruiting | N=82 --> 36 | Trial completion date: Apr 2021 --> Feb 2022 | Trial primary completion date: Dec 2020 --> Nov 2021

The IDMC confirmed that the safety of the study was favorable with no added toxicity of HER-Vaxx and SOC chemotherapy with a favorable risk-benefit for the combination . The study has completed enrollment and final data is expected in late 2021.

IMU-131 was well tolerated and safe. The induced HER2-specific Abs and cellular responses were dose-dependent and correlated with clinical responses. The highest dose (50 µg) was recommended for further evaluation in a Phase II trial, with chemotherapy +IMU-131 or chemotherapy alone, which is currently ongoing.

IMU-131 was well tolerated and safe. The vaccine-induced HER2-specific Abs and cellular responses were dose-dependent and correlated with clinical responses. The highest dose (50 µg) was recommended for further evaluation in a Phase II trial with two arms, chemotherapy with IMU-131 vaccine or chemotherapy alone, which is currently ongoing.