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

NCT06513884 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: H-200-004
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Oropharyngeal Squamous Cell Carcinoma Recurrent

Keywords

head and neck cancer; squamous cell cancer; head and neck squamous cell carcinoma; HNSCC; oropharyngeal squamous cell carcinoma; human papillomavirus 16; HPV; programmed cell death 1 ligand 1; PD-L1; immune checkpoint inhibitor; immunotherapy; genetic vector; arenavirus

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (15)

• Progression-free survival - BICR

  Up to 7.5 years after first dose of study treatment

• Duration of response - BICR

  Up to 7.5 years after first dose of study treatment

• Disease control rate - BICR

  Up to 7.5 years after first dose of study treatment

• Progression-free survival on next-line therapy

  Up to 7.5 years after first dose of study treatment

• Objective response rate - Investigator

  Up to 7.5 years after first dose of study treatment

Study Arms (2)

HB-202/HB-201 alternating 2-vector therapy with pembrolizumab

EXPERIMENTAL

Intravenous injection of HB-202 followed by pembrolizumab alternating with HB-201 followed by pembrolizumab.

Drug: HB-202/HB-201 alternating 2-vector therapy; Drug: Pembrolizumab

Matched placebo with pembrolizumab

PLACEBO COMPARATOR

Intravenous injection of matched placebo for HB-202 followed by pembrolizumab alternating with matched placebo for HB-201 followed by pembrolizumab.

Drug: Placebo; Drug: Pembrolizumab

Interventions

HB-202/HB-201 alternating 2-vector therapy DRUG

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.

Also known as: 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

HB-202/HB-201 alternating 2-vector therapy with pembrolizumab

Placebo DRUG

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.

Also known as: Matched placebo

Matched placebo with pembrolizumab

Pembrolizumab DRUG

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.

Also known as: Keytruda®

HB-202/HB-201 alternating 2-vector therapy with pembrolizumab; Matched placebo with pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hookipa Biotech GmbH: lead

MeSH Terms

Conditions

Head and Neck Neoplasms; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma, Squamous Cell; Carcinoma

Study Officials

• Head of Clinical Development

  Hookipa Biotech GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2024
• First Posted: July 22, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): April 1, 2032
• Last Updated: June 22, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share