Phase II Trial of HER-Vaxx, a B-cell Peptide-Based Vaccine, in HER2-Overexpressing Advanced Gastric Cancer Patients Under Platinum-Based Chemotherapy (HERIZON)

Author:

Tobias Joshua1ORCID,Maglakelidze Marina2ORCID,Andrić Zoran3ORCID,Ryspayeva Dinara4ORCID,Bulat Iurie5ORCID,Nikolić Ivan6ORCID,Petrović Zoran7ORCID,Chawla Tanuj8ORCID,Nagarkar Rajnish9ORCID,Garner-Spitzer Erika1ORCID,Zielinski Christoph C.10ORCID,Chong Leslie Mi Ok11ORCID,Nixon Bonnie11ORCID,Ede Nicholas J.11ORCID,Yavrom Sharon11ORCID,Kundi Michael1ORCID,Wiedermann Ursula1ORCID

Affiliation:

1. Medical University of Vienna, Vienna, Austria. 1

2. ARENSIA Exploratory Medicine LLC, Tbilisi, Georgia. 2

3. Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia. 3

4. ARENSIA Exploratory Medicine LLC, Kyiv, Ukraine. 4

5. ARENSIA Exploratory Medicine Research Unit, Institute of Oncology, Chisinau, Republic of Moldova. 5

6. Oncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia. 6

7. Military Medical Academy, Belgrade, Serbia. 7

8. Tata Medical Centre, Kolkata, India. 8

9. CG Manavata Cancer Centre, Nashik, India. 9

10. Central European Cancer Center, Wiener Privatklinik, Central European Cooperative Oncology Group (CECOG), Vienna, Australia. 10

11. Imugene Limited, Sydney, Australia. 11

Abstract

Abstract Purpose: A multicenter, randomized, open-label, phase II study (HERIZON; NCT02795988) was conducted to evaluate the clinical and immunologic efficacy of HER-Vaxx (IMU-131), a B-cell, peptide-based vaccine targeting HER2 overexpressed in 6% to 30% of gastroesophageal adenocarcinomas (GEA). Patients and Methods: Patients (n = 36) with GEA were treated with standard-of-care chemotherapy (n = 17) or HER-Vaxx plus chemotherapy (n = 19), using the recommended phase 2 dose for the vaccine. Overall survival (OS; primary endpoint), safety, progression-free survival (PFS), clinical response (secondary endpoints), and vaccine-induced HER2-specific antibody levels in serum and correlation with tumor response rates (exploratory endpoints) were investigated. Results: A 40% OS benefit [HR, 0.60; median OS, 13.9 months; 80% confidence interval (CI), 7.52–14.32] for patients treated with HER-Vaxx plus chemotherapy compared with OS of 8.31 months (80% CI, 6.01–9.59) in patients that received chemotherapy alone. A 20% PFS difference was obtained for the vaccination arm (HR, 0.80; 80% CI, 0.47, 1.38). No additional toxicity due to HER-Vaxx was observed. The vaccine-induced high levels of HER2-specific total IgG and IgG1 antibodies (P < 0.001 vs. controls) that significantly correlated with tumor reduction (IgG, P = 0.001; IgG1, P = 0.016), had a significant capacity in inhibiting phosphorylation of the intracellular HER2-signaling pathways, mediated antibody-dependent cellular cytotoxicity, and decreased immunosuppressive FOXP3+ regulatory T cells. Conclusions: 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 with 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.

Publisher

American Association for Cancer Research (AACR)

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