1421P - 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)

Background

HER2, a member of the epidermal growth factor receptor (EGFR) family, is overexpressed in approximately 30% of gastric cancers. HER-Vaxx is a B cell peptide-based anti-HER2 vaccine (IMU-131) comprising trastuzumab’s binding site. Here, we present the final results of the randomized open-label, multicenter phase 2 HERIZON trial (NCT02795988), which compared HER-Vaxx plus chemotherapy to chemotherapy alone.

Methods

Patients (n=36) with HER2-overexpressing gastric/gastro-esophageal junction cancer naïve to anti HER2 therapy, were treated with standard-of-care chemotherapy (n=17) or HER-Vaxx plus chemotherapy (n=19), using the recommended Phase 2 dose of HER-Vaxx. The study evaluated overall survival (OS; primary endpoint), safety, progression-free survival (PFS), clinical response (secondary endpoints), and vaccine-induced, HER2-specific antibody levels in serum and their correlation with tumor response rates (exploratory endpoints).

Results

A 40% OS benefit (hazard ratio [HR]: 0.60; median OS: 13.9 months; 80% confidence interval [CI]: 7.52-14.32) was observed in vaccinated patients compared with OS of 8.31 months (80% CI: 6.01-9.59) chemotherapy-alone patients. No additional toxicity due to HER-Vaxx was observed. A 20% improvement in PFS was obtained for the vaccination arm (HR: 0.80; 2-sided 80% CI:0.467, 1.381). A highly significant HER2-specific IgG and IgG1 antibody response at all time points, particularly after 3 or more doses of HER-Vaxx were induced (P<0.001), which significantly correlated with mediating ADCC and anti-tumor effects. The HER-Vaxx-induced IgG antibodies decreased levels of Foxp3+ Tregs, and exhibited a strong capacity to inhibit HER2 signalling pathway kinases Akt and MAPK phosphorylation.

Conclusions

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 trial identification

NCT02795988.

Editorial acknowledgement

Legal entity responsible for the study

Imugene, Ltd.

Funding

Has not received any funding.

Disclosure

C.C. Zielinski: Other, Personal, Other, Consultant: Athenex, MSD, AstraZeneca, Servier, Eli Lilly; Other, Personal, Other, Patents: Imugene Limited; Other, Institutional, Other: BMS, MSD, Pfizer, AstraZeneca, Merck KGaA, Amgen, Servier, Eli Lilly, Takeda, Daiichi Sankyo, Roche, Boehringer Ingelheim, Celgene, Halozyme. L.O. Chong: Financial Interests, Personal, Leadership Role: Imugene Limited. B. Nixon: Financial Interests, Personal, Stocks/Shares: Imugene Limited; Financial Interests, Personal, Full or part-time Employment: Imugene Limited; Financial Interests, Personal, Other, Spouse/Financial dependent: Imugene Limited. S. Yavrom: Financial Interests, Personal, Full or part-time Employment: Imugene Limited. N.J. Ede: Financial Interests, Personal, Full or part-time Employment: Imugene Limited. U. Wiedermann: Other, Institutional, Other, CSO at Imugene until September 2018: Imugene Limited; Other, Institutional, Other, Funding to the Institute: GSK, Pfizer; Financial Interests, Institutional, Other, Funding to the Institute: Themis. All other authors have declared no conflicts of interest.