1536P - 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

Background

HER-Vaxx is a B cell peptide-based anti-Her2 vaccine (IMU-131) comprising B cell epitopes located within trastuzumab’s binding site. In the phase Ib HERIZON trial (NCT02795988), HER-Vaxx has been shown to be safe and to prolong progression-free survival in patients with Her2-overexpressing gastric/gastro-oesophageal junction cancer (GC). The present randomized phase II open-label, multicentre study, compared two different doses of HER-Vaxx plus chemotherapy vs chemotherapy alone and aimed to evaluate antibody and clinical responses in patients with advanced or metastatic Her2-overexpressing GC naïve to Her2 therapy.

Methods

Patients were randomized to chemotherapy alone (n=17) or HER-Vaxx (50μg dose, n=19; 100μg, n=7) plus chemotherapy. In both vaccination groups, the patients received the vaccine at days 0, 14, 35, and 77 followed by q. 63 days until disease progression. Chemotherapy consisted of oxaliplatin plus capecitabine and was started at day 0, repeated q. 21 days for a maximum of 6 cycles. Specific anti-Her2 IgG antibody levels in the patient’s sera were evaluated by ELISA and clinical responses were assessed by RECIST 1.1 criteria.

Results

Evaluation of the vaccine’s two doses showed no difference in the induced Her2-specific IgG and IgG1 antibody responses, which, compared to patients from the chemotherapy-only group, were both significantly elevated (P<0.001) at all time points after 3 or more vaccinations. No further reduction of tumour diameters was observed with the vaccine’s higher dose, and the induced Her2-specific antibodies following vaccination with either dose significantly correlated with the anti-tumour effect (IgG, P=0.001; IgG1, P=0.016). 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 trial identification

NCT02795988.

Editorial acknowledgement

Legal entity responsible for the study

Imugene Limited.

Funding

Has not received any funding.

Disclosure

C. Zielinski: Other, Personal, Other, Consultancies and Speaker’s Honoraria: 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, N. Ede: Financial Interests, Personal, Full or part-time Employment: Imugene Limited. U. Wiedermann: Other, Personal, Other, CSO of Imugene until September 2018; Patents: Imugene Limited; Other, Institutional, Other, Funding to the Institute: GSK, Pfizer, Themis. All other authors have declared no conflicts of interest.