HER-Vaxx Plus Chemotherapy Improves OS in HER2+ Advanced Gastric/GEJ Cancer

The addition of the HER2-Vaxx vaccine to standard-of-care (SOC) chemotherapy led to a significant improvement in overall survival (OS) vs SOC chemotherapy alone in patients with HER2-neu overexpressing advanced and metastatic gastric and gastroesophageal junction cancer, according to findings from the final analysis of the phase 2 HERIZON trial (NCT02795988).¹

The results showed a 41.5% reduction in the risk of death with HER-Vaxx plus SOC chemotherapy vs SOC chemotherapy alone (HR, 0.585; 80% 2-sided CI, 0.368-0.930; P = .066), favoring historical data from the phase 3 ToGA trial (NCT01041404), which resulted in a hazard ratio of 0.65 with trastuzumab (Herceptin) plus chemotherapy vs chemotherapy alone in the same patient population of patients included in the HER-Vaxx study.

“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,” Tanuj Chawla, MD, the principal investigator of the HERIZON study, stated in a press release.

HER-Vaxx is a B-cell peptide cancer immunotherapy designed to treat tumors that overexpress the HER2-neu receptor. The immunotherapy, constructed from B-cell epitopes derived from the extracellular domain of HER2-neu, has demonstrated potent polyclonal antibody responses to HER2-neu in preclinical, phase 1, and now phase 2 trials.

“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,” Leslie Chong, MD, chief executive officer of Imugene, stated in a press release.

The phase 1b/2, open-label, multicenter, dose-escalation study enrolled 36 patients with HER2-neu overexpressing metastatic or advanced stomach or GEJ adenocarcinoma.²

Eligible patients were at least 20 years of age with a life expectancy of 12 weeks and an ECOG performance status between 0 and 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. Prior chemotherapy or radiotherapy for advanced gastric or GEJ cancer within 6 months of day 0 dosing was prohibited in the phase 1b cohort. Notably, men and women were required to use contraception throughout the study.

In the phase 1b portion of the study, patients in the experimental arm received 10, 30, or 50 μg of HER-Vaxx plus 80 mg/m² of cisplatin on the first day of each cycle and 4000 mg/m² of 5-fluorouracil (5-FU) administered in 100 mg/m² doses for 96 hours on days 1 and 4 of each cycle, or 2000 mg/m² of capecitabine daily for 14 days.

In the phase 2 portion of the study, patients in the experimental arm received 50 μg of HER-Vaxx plus cisplatin and 5-FU; or capecitabine; or oxaliplatin and capecitabine. Cisplatin was administered at a dose of 80 mg/m² on day 1 of each cycle, and 4000 mg/m² of 5-FU was administered for 96 hours on days 1 to 4 of each cycle at 1000 mg/m² doses each day. Treatment with capecitabine was administered at 2000 mg/m² per day for 14 days. Patients who opted for later combination chemotherapy regimen received 130 mg/m² of oxaliplatin on day 1 of each cycle plus 2000 mg/m² of capecitabine per day for 14 days.

The primary end point was OS, and the secondary end point was progression-free survival. Safety, tolerability, and immune response were also analyzed.

Notably, the longest-treated patients remain alive 2.5 years after starting therapy and generated the strongest levels of anti-HER2 antibodies from their dosing schedule on HER-Vaxx.

Additionally, no difference in safety events occurred between the treatment arms.

The HERIZON-extension Cohort Review Committee announced that a new higher 100 μg dose of HER-Vaxx has been approved for use in the phase 2 nextHERIZON trial (NCT05311176) in pretreated metastatic HER2-positive gastric cancer and the neoHERIZON trial in perioperative HER2-positive gastric cancer.

The committee determined that the 100 μg dose of HER-Vaxx was safe with no dose-limiting toxicities and no serious adverse reactions. The higher dose is expected to generate improved clinical responses for HER-Vaxx.

References

1. Imugene Presents Final HER-Vaxx Overall Survival Results In Randomized Phase 2 Trial In Advanced Gastric Cancer. News release. Imugene Limited. June 27, 2022. Accessed June 28, 2022. https://bit.ly/39Z60ac
2. A study of IMU-131(HER-Vaxx) and chemotherapy compared to chemotherapy only in patients with HER2 positive advanced gastric cancer. Updated January 20, 2022. Accessed June 28, 2022. https://clinicaltrials.gov/ct2/show/NCT02795988