74MO - 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

Background

Active immunization with the B-lymphocyte stimulating HER2 vaccine, IMU-131 (HER-Vaxx), has shown clinical response correlated with HER2-specific antibodies (Wiedermann et. al., Annals of Oncology, 2019). The IMU-131 HERIZON study is based on the landmark ToGA study (Bang et. al., The Lancet, 2010) and included patients with HER2/neu overexpressing metastatic or advanced gastric/GEJ cancer who were naïve to HER2 therapy.

Methods

Patients were randomized to IMU-131 plus standard chemotherapy or standard chemotherapy alone. The IMU-131 plus chemotherapy group received 50 μg dose of IMU-131 at Days 0, 14, 35, 77 and then every 63 days. Both groups received chemotherapy starting at Day 0 and then every 21 days for a maximum of 6 cycles. Treatment contined until disease progression or withdrawal. Chemotherapy consisted of cisplatin + 5FU or capecitabine, or oxaliplatin + capecitabine. The primary endpoint was overall survival (OS) and a total of 36 patients were randomized with a pre-specified 1-sided false positive probability of 0.10.

Results

Of 36 patients randomized (19 treated with IMU-131 plus chemotherapy and 17 with chemotherapy alone), 32 patients had a survival event (15 and 17 respectively). Analysis showed a 42% survival benefit for patients treated with IMU-131 plus chemotherapy compared to chemotherapy alone. This translated into an overall survival HR of 0.580 (80% 2-sided CI: 0.362, 0.927) with a statistically significant p-value of 0.066 (alpha 0.10). The median OS for patients receiving IMU-131 plus chemotherapy was 13.9 months, compared to 8.3 months in patients treated with chemotherapy alone. There was no difference in safety between the two treatment arms, indicating IMU-131 does not add toxicity to chemotherapy. IMU-131 induced persistent HER2 specific antibodies. 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 trial identification

IMU.ACS.001/ NCT02795988.

Editorial acknowledgement

Legal entity responsible for the study

Imugene Limited.

Funding

Imugene Limited.

Disclosure

M. Maglakelidze: Financial Interests, Institutional, Principal Investigator: Imugene Limited. D. Ryspayeva: Financial Interests, Institutional, Principal Investigator: Imugene Limited. Z.G. Andric: Financial Interests, Institutional, Principal Investigator: Imugene Limited. Z. Petrovic: Financial Interests, Institutional, Principal Investigator: Imugene Limited. I.V. Bulat: Financial Interests, Institutional, Principal Investigator: Imugene Limited. I.V. Nikolic: Financial Interests, Institutional, Principal Investigator: Imugene Limited. T. Chawla: Financial Interests, Institutional, Principal Investigator: Imugene Limited. R. Nagarkar: Financial Interests, Institutional, Principal Investigator: Imugene Limited. U. Wiedermann: Financial Interests, Institutional, Funding: Imugene Limited; Financial Interests, Institutional, Royalties: Imugene Limited; Financial Interests, Personal, Advisory Board: Imugene Limited. B.A. Blumenstein: Financial Interests, Personal and Institutional, Advisory Role: Imugene Limited. L.M.O. Chong: Financial Interests, Personal, Full or part-time Employment: Imugene Limited; Financial Interests, Personal, Member of the Board of Directors: Imugene Limited; Financial Interests, Personal, Stocks/Shares: Imugene Limited; Financial Interests, Institutional, Royalties: Imugene Limited. N.J. Ede: Financial Interests, Personal, Full or part-time Employment: Imugene Limited; Financial Interests, Personal, Officer: Imugene Limited; Financial Interests, Personal, Stocks/Shares: Imugene Limited; Financial Interests, Personal and Institutional, Royalties: Imugene Limited. B. Nixon: Financial Interests, Personal, Full or part-time Employment: Imugene Limited; Financial Interests, Personal, Stocks/Shares: Imugene Limited; Financial Interests, Institutional, Royalties: Imugene Limited. A.J. Good: Financial Interests, Personal, Full or part-time Employment: Imugene Limited; Financial Interests, Personal, Stocks/Shares: Imugene Limited ; Financial Interests, Institutional, Royalties: Imugene Limited; Financial Interests, Personal, Project Lead: Imugene Limited.