HERIZON: A phase 2 study of HER-Vaxx (IMU-131), a HER2-targeting peptide vaccine, plus standard of care chemotherapy in patients with HER2-overexpressing metastatic or advanced gastric/GEJ adenocarcinoma— Overall survival analysis.

Abstract

289 Background: Active immunization with the B-lymphocyte stimulating HER2 vaccine, HER-Vaxx (IMU-131), has shown clinical response correlated with HER2-specific antibodies (Wiedermann et. al., Clinical Cancer Research, 2021). The HER-Vaxx HERIZON study is based on the landmark ToGA study (Bang et. al., The Lancet, 2010) and included patients with HER2/neu over-expressing metastatic or advanced gastric/GEJ adenocarcinoma who were naïve to HER2 therapy. Methods: Thirty-six patients were randomized to either HER-Vaxx plus standard chemotherapy or standard chemotherapy alone. The primary endpoint was overall survival (OS). HER-Vaxx plus chemotherapy treated patients received 50 µg dose of HER-Vaxx by intra-muscular injection at Days 0, 14, 35, 77 and every 63 days until disease progression. Both groups received chemotherapy starting at Day 0 and then every 21 days for a maximum of 6 cycles or until disease progression. Standard chemotherapy consisted of cisplatin + 5FU or capecitabine, or oxaliplatin + capecitabine. Statistical analysis pre-specified a 1-sided false positive probability of 0.10. Results: Of 36 patients randomized (19 treated with HER-Vaxx plus chemotherapy and 17 with chemotherapy alone), 32 patients had a survival event (15 and 17 respectively) at the time of final analysis. All patients received oxaliplatin + capecitabine chemotherapy. Analysis showed a 42% survival benefit for patients treated with HER-Vaxx plus chemotherapy compared to chemotherapy alone. This translated into an OS HR of 0.580 (80% 2-sided CI: 0.362, 0.927) with a statistically significant p-value of 0.066. The median OS for patients receiving HER-Vaxx plus chemotherapy was 13.9 (7.5, 14.3) months, compared to 8.3 (6.0, 9.6) months in patients treated with chemotherapy alone. Median duration of response was 30 vs 19 weeks in favor of the HER-Vaxx arm. There was no difference in safety between the two treatment arms, indicating HER-Vaxx does not add toxicity to standard chemotherapy. HER-Vaxx induced persistent HER2 specific antibodies which correlated with clinical response. Additional response parameters including DOR and biomarker data will be presented at the meeting. Conclusions: 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 .

HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments

“…The vaccine consists of three fused B-cell epitopes from the HER2 extracellular domain coupled to the diphtheria toxoid and combined with the adjuvant montanide [114]. In the phase II HERIZON study, CAPOX plus HER-Vaxx improved the outcome compared to CAPOX alone in HER2-positive gastric adenocarcinoma naïve to HER2-targeting therapy [115]. The addition of HER-Vaxx resulted in a 42% survival benefit (HR 0.58, p = 0.066) and a median OS of 13.9 months (vs. 8.3 months for chemotherapy alone).…”

An Ailment with Which I Will Contend: A Narrative Review of 5000 Years of Esophagogastric Cancers and Their Treatments, with Special Emphasis on Recent Advances in Immunotherapeutics

“…Anti-HER2 vaccine therapy, hearkening back to the earliest IO experiments with less targeted vaccines in the early 20th century, is beginning to mature. The first overall survival data for HER-Vaxx (IMU-131) were published in the preliminary HERIZON study results, demonstrating overall survival of 13.9 months with HER-Vaxx with chemotherapy vs. 8.3 months for chemotherapy alone, in the second-line setting for advanced HER2+ GC and GEJC [73]. ORIENT-16, sintilimab + chemotherapy vs. chemotherapy, AC.…”

“…HERIZON study, HER-Vaxx (IMU-131) + chemotherapy, metastatic or advanced HER2+ GC and GEJC. mOS 13.9 mo for vaccine+chemotherapy vs. 8.3 mo for chemotherapy alone [73].…”

HER2 Targeting in Esophagogastric Cancer: Redefining the Landscape and Breaking Barriers

“…42 HER-Vaxx, which consists of 3 fused B-cell epitopes from the HER2-neu extracellular domain coupled to CRM197 and Th1-driving adjuvant montanide, was recently found to induce a robust immune response and improve OS when added to chemotherapy compared with chemotherapy alone. 43,44 HER-Vaxx is currently being evaluated in combination with chemotherapy and immune checkpoint blockade (NCT05311176). The TAEK-VAC-HerBy vaccine is currently being evaluated in first-in-human studies in patients with refractory disease both as monotherapy and in combination with anti-HER2 antibodies (NCT04246671).…”