Trial Title:
A Phase 2/3 Study of HB-202/HB-201 With Pembrolizumab in Patients With HPV16+ Recurrent/Metastatic Oropharyngeal Cancer
NCT ID:
NCT06513884
Condition:
Oropharyngeal Squamous Cell Carcinoma Recurrent
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Recurrence
Pembrolizumab
Conditions: 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
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
HB-202/HB-201 alternating 2-vector therapy
Description:
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.
Arm group label:
HB-202/HB-201 alternating 2-vector therapy with pembrolizumab
Other name:
HB-202 intravenous administration alternating with HB-201 intravenous administration
Other name:
HB-201 & HB-202 two-vector therapy
Other name:
TheraT® Vector(s) Expressing Human Papillomavirus 16 Positive (HPV16+) Specific Antigens
Intervention type:
Drug
Intervention name:
Placebo
Description:
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.
Arm group label:
Matched placebo with pembrolizumab
Other name:
Matched placebo
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
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.
Arm group label:
HB-202/HB-201 alternating 2-vector therapy with pembrolizumab
Arm group label:
Matched placebo with pembrolizumab
Other name:
Keytruda®
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.
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.
Criteria for eligibility:
Criteria:
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]).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
November 2024
Completion date:
April 2032
Lead sponsor:
Agency:
Hookipa Biotech GmbH
Agency class:
Industry
Source:
Hookipa Biotech GmbH
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06513884
