A Study of HB-202/HB-201 With Pembrolizumab in Patients With HPV16+ Recurrent/Metastatic Oropharyngeal Cancer

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Oropharyngeal Squamous Cell Carcinoma Recurrent
• Intervention / Treatment: Drug: HB-202/HB-201 alternating 2-vector therapy; Drug: Pembrolizumab; Drug: Placebo

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.

Participants will be randomized to receive either HB-202/HB-201 alternating 2-vector therapy followed by pembrolizumab or matched placebo (i.e., matched to the respective viral vector) followed by pembrolizumab.

Up to 150 Investigators and study sites in North America, Europe, and other regions of the world are expected to enroll participants in this study.

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants at least 18 years of age.
• Confirmed recurrent and/or metastatic OPSCC that is considered incurable by local therapies.
• Must not have had prior systemic anticancer therapy, including investigational therapy and non-palliative radiotherapy, administered in the recurrent and/or metastatic setting.
• Confirmed HPV16+ AND PD-L1+ (with a CPS greater or equal to 20) tumor, based on tumor specimen, core, or excisional biopsy samples from a tumor lesion not previously irradiated.
• Must have measurable disease based on RECIST version 1.1 as determined by BICR.
• Eastern Cooperative Oncology Group performance status must be 0 to 1.
• Adequate organ function should be confirmed within 10 days prior to the first dose of study treatment.

Exclusion Criteria:

• Has progressive disease within 6 months of completion of curatively intended systemic treatment (including checkpoint inhibitors) for locoregionally advanced OPSCC.
• Life expectancy of less than 3 months and/or rapidly progressing disease, high burden of visceral metastatic disease, or significant tumor burden in anatomically critical areas (e.g., causing significant biliary or respiratory obstruction) who may benefit from a chemotherapy-based treatment regimen.
• History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the trial or interfere with the participant's participation for the full duration of the trial, or such that it is not in the best interest of the patient to participate, in the opinion of the treating Investigator. This includes active cardiovascular disease within 6 months before study entry.
• Is pregnant or breastfeeding or expecting to conceive or father children starting with the screening visit through a minimum of 2 months after the last dose of trial treatment.
• Was discontinued due to a Grade 3 or 4 immune-related AE after receiving prior therapy with a checkpoint inhibitor agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
• Received systemic steroids at a dose of >10 mg/day (prednisone equivalent) for <30 days within 14 days or for ≥30 days within 28 days of the first dose of study treatment.
• Received live, or live-attenuated vaccine within 30 days of the planned first dose of treatment or anticipates that such a vaccine will be required during the study.
• Participating in or has participated in a study of an investigational agent, or has used an investigational device treatment, within 4 weeks before the first dose of study treatment.
• Has had an allogeneic tissue/solid organ transplant.
• Has known immunodeficiency OR is receiving long-term systemic steroid therapy or any other form of immunosuppressive therapy within 28 days before the first dose of study treatment.
• Known additional malignancy within 2 years before the first dose of study treatment.
• Known CNS metastases and/or carcinomatous meningitis.
• Has severe hypersensitivity (Grade 3 and/or 4) to pembrolizumab and/or any of its excipients.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years.
• History or current evidence of (non-infectious) pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Known history of acquired immunodeficiency syndrome (AIDS). Testing for human immunodeficiency virus (HIV) is not mandatory.
• Known history of hepatitis B virus (defined as hepatitis B surface antigen reactive) or known active hepatitis C virus infection (defined as hepatitis C virus ribonucleic acid [RNA] is detected [qualitative]).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HB-202/HB-201 alternating 2-vector therapy with pembrolizumab; Intravenous injection of HB-202 followed by pembrolizumab alternating with HB-201 followed by pembrolizumab.	Drug: HB-202/HB-201 alternating 2-vector therapy; Intravenous administration of HB-202 alternating with HB-201, with the first 2 treatment cycles administered every 3 weeks and then every 6 weeks from the third treatment cycle onwards.; Other Names: HB-202 intravenous administration alternating with HB-201 intravenous administration; HB-201 & HB-202 two-vector therapy; TheraT® Vector(s) Expressing Human Papillomavirus 16 Positive (HPV16+) Specific Antigens; Drug: Pembrolizumab; Intravenous administration of pembrolizumab, with the first 2 treatment cycles administered at a dosage of 200 mg every 3 weeks and then every 6 weeks from the third treatment cycle onwards administered at a dosage of 400 mg.; Other Names: Keytruda®
Placebo Comparator: Matched placebo with pembrolizumab; Intravenous injection of matched placebo for HB-202 followed by pembrolizumab alternating with matched placebo for HB-201 followed by pembrolizumab.	Drug: Pembrolizumab; Intravenous administration of pembrolizumab, with the first 2 treatment cycles administered at a dosage of 200 mg every 3 weeks and then every 6 weeks from the third treatment cycle onwards administered at a dosage of 400 mg.; Other Names: Keytruda®; Drug: Placebo; Intravenous administration of matched placebo for HB-202 alternating with matched placebo for HB-201, with the first 2 treatment cycles administered every 3 weeks and then every 6 weeks from the third treatment cycle onwards.; Other Names: Matched placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate - Blinded independent central review (BICR)	Objective response rate (ORR) defined as the proportion of participants with a confirmed best overall response of complete response or partial response, as assessed by BICR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	Up to 7.5 years after first dose of study treatment
Overall survival	Overall survival defined as the time from the date of randomization to the date of death from any cause.	Up to 7.5 years after first dose of study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival - BICR	Progression-free survival (PFS) defined as the time from the date of randomization to the date of progressive disease, as assessed by BICR based on RECIST version 1.1, or to the date of death from any cause, whichever occurs first.	Up to 7.5 years after first dose of study treatment
Duration of response - BICR	Duration of response (DOR) defined as the time from the date of the first objective response (complete or partial response) to the date of progressive disease as assessed by BICR based on RECIST version 1.1, or to the date of death from any cause, whichever occurs first.	Up to 7.5 years after first dose of study treatment
Disease control rate - BICR	Disease control rate (DCR) defined as the proportion of participants with a confirmed best overall response of complete response, partial response, or stable disease as assessed by BICR based on RECIST version 1.1.	Up to 7.5 years after first dose of study treatment
Progression-free survival on next-line therapy	Progression-free survival on next-line therapy defined as the time from the date of randomization to the Investigator-reported date of progression on next-line therapy, or to the date of death from any cause, whichever occurs first.	Up to 7.5 years after first dose of study treatment
Objective response rate - Investigator	ORR defined as the proportion of participants with a confirmed best overall response of complete response or partial response, as assessed by the Investigator based on RECIST version 1.1 and immune RECIST (iRECIST).	Up to 7.5 years after first dose of study treatment
Progression-free survival - Investigator	PFS defined as the time from the date of randomization to the date of progressive disease, as assessed by the Investigator based on RECIST version 1.1 and iRECIST, or to the date of death from any cause, whichever occurs first.	Up to 7.5 years after first dose of study treatment
Duration of response - Investigator	DOR defined as the time from the date of the first objective response (complete or partial response) to the date of progressive disease as assessed by the Investigator based on RECIST version 1.1 and iRECIST, or to the date of death from any cause, whichever occurs first.	Up to 7.5 years after first dose of study treatment
Disease control rate - Investigator	DCR defined as the proportion of participants with a confirmed best overall response of complete response, partial response, or stable disease as assessed by the Investigator based on RECIST version 1.1 and iRECIST.	Up to 7.5 years after first dose of study treatment
Proportion of participants with AEs - overall	Overall occurrence of AEs by relationship to study treatment, type, grade, and seriousness.	Up to 7.5 years after first dose of study treatment
Adjusted on-study year rate of AEs	Adjusted on-study yearly rate of AEs by relationship to study treatment, type, grade, and seriousness.	Up to 7.5 years after first dose of study treatment
Proportion of participants with laboratory abnormality - overall	Overall occurrence of laboratory abnormality by laboratory test.	Up to 2 years after first dose of study treatment
Adjusted on-study yearly rate of laboratory abnormality	Adjusted on-study yearly rate of laboratory abnormality by laboratory test.	Up to 2 years after first dose of study treatment
Participant-reported health-related quality of life - European Quality of Life scale EQ-5D-3L	European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L) score by dimension and item.	Up to 7.5 years after first dose of study treatment
Participant-reported health-related quality of life - EORTC QLQ-C30	European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) score by scale and item.	Up to 7.5 years after first dose of study treatment
Participant-reported health-related quality of life - EORTC QLQ-H&N35	European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Cancer module 35 (EORTC QLQ-H&N35) score by scale and item.	Up to 7.5 years after first dose of study treatment

Collaborators and Investigators

• Sponsor: Hookipa Biotech GmbH
• Investigators: Study Director: Head of Clinical Development, Hookipa Biotech GmbH

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): April 1, 2032

Study Registration Dates

• First Submitted: July 17, 2024
• First Submitted That Met QC Criteria: July 17, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): June 22, 2025
• Last Update Submitted That Met QC Criteria: June 20, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: immunotherapy; PD-L1; head and neck cancer; HNSCC; oropharyngeal squamous cell carcinoma; head and neck squamous cell carcinoma; HPV; immune checkpoint inhibitor; squamous cell cancer; human papillomavirus 16; programmed cell death 1 ligand 1; arenavirus; genetic vector
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Recurrence; Carcinoma; Carcinoma, Squamous Cell; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: H-200-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No