In patients with HER-2/Neu-overexpressing advanced/metastatic gastric or gastroesophageal junction (GEJ) cancer, HER-Vaxx (IMU-131) added to standard of care (SOC) chemotherapy demonstrated a 41.5% survival benefit compared with SOC chemotherapy alone.1
HER-Vaxx is a single peptide structure that contains 3 individual B-cell epitope peptide sequences chosen from HER2/neu structure. The vaccine blocks HER2 signaling pathways, and it appears to be better than treatment with trastuzumab (Herceptin) monotherapy.
According to findings from HERIZON clinical trial (NCT02795988), the hazard ratio for overall survival (OS) observed with HER-Vaxx and SOC was 0.585 (80% 2-sided CI, 0.368-0.930. The P-value was statistically significant at 0.066. The findings also suggested that HER-Vaxx does not add toxicity to SOC chemotherapy based on similar adverse events (AEs) observed between the treatment arms,
“I am delighted to report that we have achieved this significant milestone for patients with advanced gastric cancer. The final analysis favored the survival outcome for HER-Vaxx and I note the Independent Data Monitoring Committee previously suggested to shorten the study by lowering the number of patients, said Leslie Chong, medical director and chief executive officer of Imugene,” in a press release.
HERIZON is a phase 1b/2, open-label study of 36 patients with HER2/Neu overexpressing metastatic or advanced adenocarcinoma of the stomach or GEJ. Patients in the experimental phase 1b arm received either 10, 30, or 50μg of HER-Vaxx in combination with cisplatin 80 mg/m2 on the first day of each cycle and fluorouracil (5-FU) 4000 mg/m2 administered in 100 mg/m2 doses for 96 hours on days 1 and 4 of each cycle, or capecitabine 2000 mg/m2 per day for 14 days.2
Patients in the experimental phase 2 arm are treated with 50μg of HER-Vaxx in combination with cisplatin, and either 5-FU or capecitabine or oxaliplatin and capecitabine. Cisplatin 80 mg/m2 is administered to patients on day 1 of each cycle, and 5-FU4000 mg/m2 is administered for 96 hours on days 1 to 4 of each cycle at 1000 mg/m2 doses each day. Treatment with capecitabine is administered at 2000 mg/m2 per day for 14 days, and the combination of oxaliplatin 130 mg/m2 on day 1 of each cycle and capecitabine 2000 mg/m2 per day for 14 days.
In phase 1b, the study explored the coprimary end points of safety/tolerability and determined the recommended phase 2 dose of HER-Vaxx. The phase 2 primary end point of the study is the clinical efficacy of HER-Vaxx defined by overall survival (OS). Secondary end points of the phase 2 study included progression-free survival, time to progression, disease control rate, objective response rate, duration of objective response, change in tumor size, humoral and cellular immunogenicity of HER-Vaxx, and the incidence of treatment-emergent AEs.
As exploratory outcomes, HERIZON is also assessing the antibodies analyzed in serum samples taken across study visits to determine humoral immunogenicity, vaccine-specific cytokine levels, and regulatory T and B cells analyzed in whole blood samples to determine cellular immunogenicity. In addition, radiographic data measured by RECIST v1.1, measurement of serum prediction marker of tumor progression, and measurement of immunological, and biochemical markers are being evaluated as exploratory end points in the study.
Patients included in the study were aged 20 years or older with a life expectancy of 12 weeks and an ECOG performance status of 0-2. Patients were required to have at least 1 measurable lesion, along with adequate left ventricular ejection function, hematologic function, liver function, and renal function. Those included in phase 1b could not have received prior chemotherapy or radiotherapy for advanced gastric or GEJ cancer within 6 months of day 1 dosing in HERIZON. Both male and female patients were required to use contraception throughout the study.
HERIZON is ongoing at 22 study locations worldwide. Further, a HERIZON-extension Cohort Review Committee has supported the use of a 100μg dose of HER-Vaxx in the nextHERIZON clinical trial (NCT05311176), which will investigate the vaccine in pretreated patients with metastatic HER2-positive gastric cancer, as well as in the neoHERIZON trial of patients with perioperative HER2-positive gastric cancer.
1. Imugene presents final HER-Vaxx overall survival results in randomized phase 2 trial in advanced gastric cancer. News release. June 27, 2022. Accessed June 28, 2022. https://bit.ly/3HVvGRQ
2. A study of IMU-131(HER-Vaxx) and chemotherapy compared to chemotherapy only in patients with her2 positive advanced gastric cancer. Clinicaltrials.gov. Updated January 20, 2022. Accessed June 28, 2022. https://bit.ly/3OuGTuX