A Study of HB-202/HB-201 With Pembrolizumab in Patients With HPV16+ Recurrent/Metastatic Oropharyngeal Cancer
brief summary
This is a study of HB-202/HB-201 alternating 2-vector therapy with pembrolizumab (also known as Keytruda®) in people with human papillomavirus subtype 16 positive (HPV16+) head and neck cancer starting in the middle part of the throat, who have not yet received systemic treatment after their cancer spread (metastatic) and/or returned (recurrent) and who are eligible to receive pembrolizumab. Doctors already use pembrolizumab therapy (with or without chemotherapy) to treat head and neck cancer. However, the treatment does not work well in most people with this type of cancer. HB-202/HB-201 alternating 2-vector therapy with pembrolizumab, which is designated to stimulate a stronger immune attack against HPV16+ tumors, was shown to be safe and suggested to work better than pembrolizumab-only in a small number of participants with HPV16+ head and neck cancer (see H-200-001, NCT04180215). This trial studies HB-202/HB-201 alternating 2-vector therapy with pembrolizumab in a much larger number of participants from different countries to confirm its benefits for people with HPV16+ head and neck cancer that started in the middle part of the throat compared with pembrolizumab-only therapy. This trial studies whether administering HB-202/HB-201 alternating 2-vector therapy with pembrolizumab works better in more participants by shrinking their tumors and makes them live longer than pembrolizumab-only therapy. Participants will receive the study treatments by injection into a vein every 3 weeks during the first 3 months and then every 6 weeks until up to about 2 years, which will be followed by a long observation period to continue looking at the safety and clinical benefits after the last dose of study treatment.
detailed description
This is a seamless adaptive Phase 2/3, randomized, double-blinded, placebo-controlled, multicenter trial of HB-202/HB-201 alternating 2-vector therapy with the approved drug pembrolizumab in participants with HPV16+ recurrent and/or metastatic oropharyngeal squamous cell carcinoma (OPSCC), whose tumor has a programmed cell death ligand-1 (PD-L1) combined positive score (CPS) greater than or equal to 20 in the first line setting. OPSCC is a type of head and neck squamous cell carcinoma (HNSCC) originating in the oropharyngeal region (tonsil, tongue base, soft palate, or uvula). The study will evaluate the long-term safety and the benefits on objective response rate, overall survival, and progression-free survival of HB-202/HB-201 alternating 2-vector therapy plus pembrolizumab compared with pembrolizumab-only therapy.
Pembrolizumab-only therapy or pembrolizumab plus chemotherapy are currently the first-line therapies used to treat people with recurrent and/or metastatic HNSCC (including HPV+ OPSCC). However, poor prognosis prevails despite pembrolizumab therapy with or without chemotherapy (including patients with PD-L1 CPS greater or equal to 20), where only a minority of patients respond.
HB-202 and HB-201 are genetically engineered, replicating vectors based on the arenaviruses Pichinde virus and lymphocytic choriomeningitis virus, respectively. The HB-202 and HB-201 vectors have been engineered to deliver specific non-oncogenic antigens derived from HPV16, which enables the vectors to stimulate a strong and specific immune response against HPV16+ tumor cells. Pembrolizumab on the other hand is a potent checkpoint inhibitor, which binds to immune cell surface receptors to relieve the typical inhibition of immune surveillance of tumors. In an early phase trial (H-200-001, NCT04180215), HB-202/HB-201 alternating 2-vector therapy with pembrolizumab has shown favorable safety and preliminary anti-tumor activity with an objective response rate higher than previously reported with pembrolizumab-only therapy in participants with HPV16+ OPSCC.
HB-202/HB-201 alternating 2-vector therapy or matched placebo will be administered in treatment cycles. A treatment cycle is defined as one administration of HB-202 plus the post-dose period followed by one administration of HB-201 plus the post-dose period until the next dose. In the first 2 treatment cycles, the HB-202/HB-201 or matched placebo treatment is administered with 200 mg pembrolizumab every 3 weeks. The HB-202/HB-201 or matched placebo treatment is administered with 400 mg pembrolizumab every 6 weeks from the third treatment cycle onwards. Adverse events (AEs) will be monitored for up to 30 days and serious AEs for up to 90 days after the last dose of study treatment. There will be long-term follow-up every 3 months after the last administration of study treatment for all participants until the participant's death, the participant is lost to follow-up or withdraws consent to follow-up, last study-related phone call or visit, or study termination, whichever occurs first.
official title
A Randomized Double-blinded Phase 2/3 Study of HB-202/HB-201 Alternating 2-Vector Therapy With Pembrolizumab Versus Pembrolizumab-Only for First Line HPV16+ High PD-L1 CPS Recurrent and/or Metastatic Oropharyngeal Squamous Cell Carcinoma