Dr Yilmaz on HB-200 Arenavirus Plus Pembrolizumab in HPV16+ Head and Neck Cancer

Emrullah Yilmaz, MD, PhD, clinical assistant professor, Hematology and Medical Oncology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University; member, Immune Oncology Program, Case Comprehensive Cancer Center, discusses a study investigating HB-200 arenavirus–based immunotherapy plus pembrolizumab (Keytruda) in the first-line treatment of patients with recurrent/metastatic human papillomavirus type 16 (HPV16)–positive head and neck cancer.

At the 2024 ASCO Annual Meeting, investigators presented findings from the phase 2 cohort of a phase 1/2 trial (NCT04180215) that enrolled 46 patients, primarily those with oropharyngeal primary tumors and prior exposure to chemoradiation. Initial results demonstrated a manageable safety profile and clinical activity with HB-200 plus pembrolizumab. Notably, responses were more pronounced in patients with a PD-L1 combined positive score (CPS) of 20 or higher, indicating a correlation between PD-L1 expression and treatment efficacy. These findings have prompted the initiation of the randomized, phase 2/3 H-200-004 trial to further evaluate HB-200 in combination with pembrolizumab in patients with HPV16-positive oropharyngeal squamous cell carcinoma.

HPV16 is the most common subtype of the HPV virus seen in HPV-positive oropharyngeal cancer, with more than 90% of these patients having HPV16, Yilmaz begins. This prevalence is why the HB-200 arenavirus was specifically designed to target HPV16, he says. Essentially, this drug is an RNA virus vector that induces an immune response specific to HPV16, thereby enhancing the immune system’s ability to target cancer-specific cells. The aim of this phase 1/2 trial was to make immunotherapy more effective by combining the HB-200 arenavirus with pembrolizumab, he reports.

The most exciting findings from the study are the enhanced responses observed with the combination therapy compared with single-agent pembrolizumab, Yilmaz continues. For patients with a PD-L1 CPS of at least 1 (n = 35), the overall response rate (ORR) was 37.1%, and for those with a PD-L1 CPS of 20 or more (n = 17), the ORR was 52.9%, he says. Additionally, patients could tolerate the treatment for extended periods, resulting in a longer duration of response compared with single-agent immunotherapy, Yilmaz explains. These promising results highlight the potential of this combination therapy to improve outcomes for patients with HPV-positive oropharyngeal cancer, Yilmaz concludes.