Results from the phase 2 HERIZON study identified improved overall survival for patients treated with IMU-131 plus standard of care vs standard of care alone in advanced or metastatic gastric or gastroesophageal junction cancer.
Improved overall survival (OS) was observed following treatment with IMU-131 (HER-Vaxx) plus standard of care (SOC) vs SOC alone for patients with advanced or metastatic gastric or gastroesophageal junction cancer, according to results from the phase 2 HERIZON study (NCT0295988).1
This is a B-cell peptide cancer immunotherapy that was designed to target tumors that overexpress the HER2 receptor, specifically gastric, breast, ovarian, lung, and pancreatic. Additionally, this treatment was constructed from B cell epitopes from the extracellular domain of HER2.
A survival benefit of 41.5% was shown in the combination arm vs SOC alone (HR, 0.585; 80% 2-sided CI, 0.368-0.930; P = .066). Of note, there was no difference in safety between the 2 arms which shows that the combination might not add any toxicity. To date, the longest treated patients are alive 2.5 years after starting therapy, with 1 patient who has been alive for nearly 3 years from the beginning of therapy. The patients who remain alive had the strongest anti-HER2 antibody levels from the dosing schedule.
“It has been a true pleasure to be an investigator on the HERIZON clinical trial. I have seen a positive impact on the long-term survival in my patients taking HER-Vaxx and look forward to the future development of this vaccine,” principal investigator Tanuj Chawla, MD, consultant at Tata Medical Center, said in the press release.
Results from the study’s per protocol pre-planned first interim analysis were previously presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.2 A total of 27 patients were included in the analysis, of whom 8 patients had died in the SOC alone arm vs 4 in the combination arm (2-sided 80% CI, 0.186-0.942; P = .083). In the SOC alone arm, 9 patients progressed on treatment compared with 6 in the combination arm (HR, 0.532; 2-sided 80% CI, 0.267-1.060; P = .086).
Patients received SOC alone for a maximum of 6 cycles of treatment, and the combination arm received 50 μg of IMU-131 on day 0, day 14, day 35, day 77, and then every 63 days thereafter until disease progression.
The primary end points of this trial included safety and tolerability, recommended phase 2 dosing, and clinical efficacy. The secondary end points were progression-free survival, time to progression, disease control rate, and objective response rate.
Patients were eligible for the study if they were older than 20, had a life expectancy of at least 12 weeks, had metastatic or locally advanced disease not remedied by surgical resection, and had 1 measurable lesion via RECIST 1.1. Exclusion criteria included having previous treatment with trastuzumab (Herceptin) or any other HER2 targeting agent, continuous systemic treatment with corticosteroids or other immunosuppressive medications, or having a prior organ transplant.
A HERIZON-extension Cohort Review Committee was created and confirmed what a higher dose of IMU-131 at 100 μg was approved and will be used for the phase 2 nextHERIZON study (NCT05311176) for patients with pretreated metastatic HER2-positive gastric cancer, as well as the phase 1/2 neoHERIZON study (NCT02795988) for patients with perioperative HER2-positive gastric cancer. The studies will begin enrollment soon.
The Cohort Review Committee has found that the new dose not have any dose-limiting toxicities or serious toxicity. This new dose may help to strengthen antibody generation to better improve the clinical response.