Early Exploration With HER-Vaxx Extends Survival for Patients with HER2+ Gastric/GEJ Adenocarcinoma

Patients with HER2-overexpressing metastatic or advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma treated with HER-Vaxx (IMU-131) plus standard-of-care chemotherapy had a statistically significant survival benefit compared with those who received chemotherapy alone, according to results from the final overall survival (OS) analysis of the phase 1/2 HERIZON trial (NCT02795988).¹

Results, presented during the 2023 Gastrointestinal Cancers Symposium, showed that patients who received the HER2-targeted peptide vaccine in combination with chemotherapy (n = 19) had a median OS of 14.0 months (80% CI, 11.1-14.3) vs 8.3 months (80% CI, 6.0-9.59) among 17 patients treated with chemotherapy alone (HR, 0.558; 80% CI, 0.349-0.895; 1-sided P = .054). All patients in the chemotherapy-only arm experienced a survival event compared with 15 in the arm treated with the combination.

“There was statistically significant survival benefit seen in our study with patients taking HER-Vaxx,” Tanuj Chawla, MD, a medical consultant at Tata Medical Center in Delhi, India, said in a presentation of the findings. “At the time of evaluation, all 17 patients in the chemotherapy arm succumbed to their disease…in the HER-Vaxx [arm] we had 4 patients who are alive.” Chawla noted that in the Kaplan Meier curves, early suppression of the curves was observed for patients receiving HER-Vaxx. “At the tail of the curve, it’s showing that patients were alive. They were evaluated, followed-up [with], and showed immune effect.”

HER-Vaxx is a B-cell immunotherapy made up of 3 B-cell epitopes derived from the extracellular domain of HER2.¹ The peptide epitopes are conjugated to CRM197, a carrier protein, in a montanide th1 emulsion. In preclinical study, the agent stimulated a potent polyclonal antibody response to HER2.

HERIZON is an open-label, multicenter study conducted across sites in eastern Europe and India. Chawla noted that the study was performed in these areas due to the lack of access to fam-trastuzumab deruxtecan-nxki (Enhertu). Patients with treatment-naïve, HER2-positive, stage III/IV gastric/GEJ adenocarcinoma were eligible for enrollment.

Once enrolled, patients were stratified for tumor stage and randomly assigned 1:1 to receive either HER-Vaxx 50 μg via intramuscular injection at days 0, 14, 35, 77 and every 63 days until disease progression plus standard-of-care chemotherapy or standard-of-care chemotherapy alone. In both arms, patients were given chemotherapy starting at day 0, then every 21 days for a maximum of 6 cycles or until disease progression. The chemotherapy regimen consisted of cisplatin plus fluorouracil or capecitabine, or oxaliplatin plus capecitabine.¹

The primary end point was OS. Secondary end points included progression-free survival (PFS), safety, and immune response. The first patient was recruited in March 2019 and the last in January 2021, Chawla said.

Baseline patient characteristics were well-balanced between the combination and chemotherapy arms. Patients had a median age of 65 years (range, 48-84) and 68 years (range, 44-79), respectively. Most patients in both arms had an ECOG performance status of 1 or 2 (58% vs 53%), adenocarcinoma of the stomach (90% vs 88%), and stage IV disease (74% vs 77%). Prior gastric surgery was performed on 53% and 41% of patients, respectively.

Additional findings from the study showed that the median PFS was 6.93 months (80% CI, 5.6-9.9) in the arm that received the vaccine vs 6.01 months (80% CI, 2.2-8.3) in the arm treated with chemotherapy alone. Moreover, the duration of response was longer in the combination arm compared with the chemotherapy arm, at 30 weeks vs 19 weeks, respectively.

Regarding safety, treatment-emergent adverse effects (TEAEs) were reported in 95% and 94% of patients in the combination and chemotherapy-alone arms, respectively. Serious TEAEs of any grade (11% vs 29%), grade 3 or greater serious TEAEs (42% vs 42%), and treatment-related AEs (84% vs 77%) were present in both arms.

More patients in the chemotherapy-alone arm experienced a TEAE that led to treatment discontinuation compared with the combination arm, 24% vs 11%, respectively. Additionally, TEAEs leading to treatment reduction or interruption occurred at a rate of 35% and 42%, respectively.

The most common grade 1/2 adverse effects (AEs) in the combination arm included decrease appetite (26%), headache (26%), diarrhea (21%), and nausea (21%). Common grade 3 or greater AEs included fatigue (11%), anemia (5%), diarrhea (5%), and decreased platelet count (5%).¹

In the chemotherapy-alone arm, common grade 1/2 AEs included vomiting (18%), decreased platelet count (18%), and diarrhea (18%). The grade 3 or greater AEs present in this arm were anemia (24%) and decreased platelet count (6%).

One patient in each arm experienced a grade 5 TEAE. In the combination arm, the patient had a grade 5 COVID-19 infection and in the chemotherapy-alone arm there was one instance of grade 5 respiratory failure.¹

“There was no additional toxicity we observed when patients were given HER-Vaxx along with combination chemotherapy,” Chawla said. “We [are] also exploring alternative vaccine doses in a single-arm phase 2 extension study.”

Further, HER-Vaxx is under investigation in an ongoing phase 2 nextHORIZON study (NCT05311176) which will evaluate the novel therapeutic in combination with pembrolizumab (Keytruda) or ramucirumab (Cyramza) plus paclitaxel.²

References

1. Maglakelidze M, Ryspayeva, Andric Z, et al. 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. final overall survival analysis. J Clin Oncol. 2023;41(suppl 4):289. doi:10.1200/JCO.2023.41.3_suppl.289
2. A study of IMU-131 (HER-Vaxx) in combination with chemotherapy or pembrolizumab in patients with metastatic HER2/neu over-expressing gastric cancer (nextHERIZON) (nextHERIZON). ClinicalTrials.gov. Updated January 4, 2023. Accessed January 19, 2023. https://clinicaltrials.gov/ct2/show/NCT05311176