Trial Title:
pBI-11 & TA-HPV (With Pembrolizumab as Treatment for Patients w/Advanced, PD-L1 CPS≥1, hrHPV+ Oropharyngeal Cancer
NCT ID:
NCT05799144
Condition:
Metastatic Oropharyngeal Carcinoma
Recurrent Oropharyngeal Carcinoma
Conditions: Official terms:
Carcinoma
Oropharyngeal Neoplasms
Pembrolizumab
Vaccines
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
DNA Vaccine
Description:
Given pBI-11 IM
Arm group label:
Treatment (pBI-11, TA-HPV, pembrolizumab)
Intervention type:
Biological
Intervention name:
Human Papillomavirus Tumor Antigen Vaccine
Description:
Given into a muscle
Arm group label:
Treatment (pBI-11, TA-HPV, pembrolizumab)
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given into vein
Arm group label:
Treatment (pBI-11, TA-HPV, pembrolizumab)
Intervention type:
Procedure
Intervention name:
Computed Tomography (CT)
Description:
Undergo a CT
Arm group label:
Treatment (pBI-11, TA-HPV, pembrolizumab)
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging (MRI)
Description:
Undergo an MRI
Arm group label:
Treatment (pBI-11, TA-HPV, pembrolizumab)
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo blood sample collection
Arm group label:
Treatment (pBI-11, TA-HPV, pembrolizumab)
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo tumor biopsy
Arm group label:
Treatment (pBI-11, TA-HPV, pembrolizumab)
Summary:
This phase II trial tests how well pB1-11 and human papillomavirus tumor antigen (TA-HPV)
vaccines in combination with pembrolizumab work in treating patients with oropharyngeal
cancer that has come back (recurrent) or that has spread from where it first started
(primary site) to other places in the body (metastatic) and that is PD-L1 and human
papillomavirus (HPV) positive. Oropharyngeal cancer is a type of head and neck cancer
involving structures in the back of the throat (the oropharynx), such as the non-bony
back roof of the mouth (soft palate), sides and back wall of the throat, tonsils, and
back third of the tongue. Scientists have found that some strains or types of a virus
called HPV can cause oropharyngeal cancer. pBI-11 is a circular deoxyribonucleic acid
(DNA) (plasmid) vaccine that promotes antibody, cytotoxic T cell, and protective immune
responses. TA-HPV is an investigational recombinant vaccina virus derived from a strain
of the vaccina virus which was widely used for smallpox vaccination. Vaccination with
this TA-HPV vaccine may stimulate the immune system to mount a cytotoxic T cell response
against tumor cells positive for HPV, resulting in decreased tumor growth. Immunotherapy
with monoclonal antibodies, such as pembrolizumab, may help the body's immune system
attack the cancer, and may interfere with the ability of tumor cells to grow and spread
by inhibiting the PD-1 receptor. These investigational vaccines could cause or enhance an
immune response in the body against HPV, during which time the activity of pembrolizumab
against oropharyngeal cancer associated with HPV may be strengthened. These drugs in
combination may be more effective in increasing the ability of the immune system to fight
oropharyngeal cancer than pembrolizumab alone.
Detailed description:
PRIMARY OBJECTIVE:
I. To assess the safety and feasibility of intramuscular PVX7 (pBI-11/pBI-11/human
papillomavirus tumor antigen vaccine [TA-HPV]) immunization in patients with HPV+
recurrent/metastatic (R/M) oropharyngeal carcinoma (OPC) undergoing treatment with
pembrolizumab.
SECONDARY OBJECTIVE:
I. To assess the response rate (RR) of the addition of pBI-11 and TA-HPV to pembrolizumab
(P) as first line therapy for patients with PD-L1+ (combined positive score [CPS] >= 1),
HPV+, R/M OPC.
EXPLORATORY OBJECTIVES:
I. To evaluate the overall survival (OS), progression free survival (PFS) and safety of
the combination of PVX7 and pembrolizumab in this population.
II. To evaluate correlates of clinical activity by: (1) comparing HPV16/18 E6/E7-specific
cellular and humoral immunity in pre- versus (vs.) post-pBI-11 and TA HPV-treated OPC
patients that are pembrolizumab responders (R) and/or non-responders (NR).
OUTLINE:
Patients receive pBI-11 vaccine intramuscularly (IM), TA-HPV vaccine IM, and
pembrolizumab intravenously (IV) on study. Patients undergo computed tomography (CT) or
magnetic resonance imaging (MRI) and blood sample collection during screening and on
study. Patients may undergo tumor biopsy during screening and on study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Signed and dated written informed consent
- Male or female >= 18 years of age on the day of signing informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Having been diagnosed with R/M p16+ PD-L1 CPS >= 1 OPC not previously treated for
R/M disease. They must be eligible for, and planning to start therapy with
pembrolizumab, according to standard of care
- hrHPV(+) status (staining with p16 is adequate) and PD-L1 expression (CPS≥1) in
tumor based on validated testing methods performed on FFPE tumor tissue (needle core
biopsy or resection; fine needle aspiration/biopsy [FNA] cell blocks acceptable if
with adequate tissue) at local labs or VUMC labs. [This biopsy tissue will also be
used for the pre-treatment tissue research correlate studies.] For patients with
neither existing tumor hrHPV and PD-L1 CPS test results nor adequate archived tissue
available for PD-L1 and hrHPV testing, a biopsy performed during screening is
necessary to obtain diagnostic tissue. If no tissue is available for PD-L1 and hrHPV
testing on either archived or newly obtained tissue, the patient cannot be enrolled.
- Evaluable tumor burden (measurable and/or non-measurable tumor lesion[s]) which can
be followed by computed tomography (CT) scan or magnetic resonance imaging (MRI),
based on Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST) as
assessed by the local site investigator/radiology. Tumors that are biopsied (for
diagnosis and research use) will not be considered in the iRECIST version (v)1.1
assessment. However, if patient has only one evaluable tumor, patient may still be
eligible for participation
- Absolute neutrophil count (ANC) >= 1,000/uL (resulted =< 28 days prior to first dose
of protocol-indicated treatment)
- CD4 T cell count > 200/uL (resulted =< 28 days prior to first dose of
protocol-indicated treatment)
- Platelets >= 75,000/uL (resulted =< 28 days prior to first dose of
protocol-indicated treatment)
- Hemoglobin >= 7.0 g/dL (resulted =< 28 days prior to first dose of
protocol-indicated treatment)
- Estimated glomerular filtration rate (eGFR) >= 45 mL/min (as calculated by the
Cockcroft-Gault Formula or calculated/measured by an alternative established
institutional standard consistently applied across participants at the site)
(resulted =< 28 days prior to first dose of protocol-indicated treatment)
- Total bilirubin =< 1.5 times institutional upper limit of normal (ULN), or direct
bilirubin =< ULN for participants with total bilirubin > 1.5 x ULN (resulted =< 28
days prior to first dose of protocol-indicated treatment)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])
and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =<
2.5 times institutional ULN (resulted =< 28 days prior to first dose of
protocol-indicated treatment)
- Calcium =< 11.5 mg/dL or =< 2.9 mmol/L; in patients with albumin outside the normal
range, calcium (corrected for albumin) must be =< 11.5 mg/dL or =< 2.9 mmol/L
(resulted =< 28 days prior to first dose of protocol-indicated treatment)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 times
institutional ULN; except for patients receiving anticoagulant therapy as long as PT
in such patients per investigator judgment is within therapeutic range of intended
use of anticoagulants (resulted =< 28 days prior to first dose of protocol-indicated
treatment)
- Activated partial thromboplastin time (aPTT) preferred or partial thromboplastin
time (PTT) =< 1.5 times institutional ULN; except for patients receiving
anticoagulant therapy as long as PTT in such patients per investigator judgment is
within therapeutic range of intended use of anticoagulants (resulted =< 28 days
prior to first dose of protocol-indicated treatment)
- Patients must not be breastfeeding and further agree to not breastfeed during study
treatment; and for at least 120 days after patient's final dose of heterologous
vaccination and pembrolizumab
- A woman of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test during screening within 28 days prior to receiving first dose of
protocol-indicated treatment, and must agree to follow instructions for using
acceptable contraception from the time of signing consent, and until at least 180
days after her final dose of heterologous vaccination and pembrolizumab. In order to
be considered not of childbearing potential, women under the age of 62 must have a
documented serum follicle stimulating hormone (FSH) level more than 40 mIU/mL (or
within local laboratory reference range for postmenopausal women
- Patients must refrain from donating blood or sperm throughout the duration of study
treatment followed by at least 120 days after patients' final dose of heterologous
vaccination or pembrolizumab
- A patient able to father children who is sexually active with a WOCBP must agree to
follow instructions for using acceptable contraception, from the time of signing
consent, and until at least 120 days after his final dose of heterologous
vaccination and pembrolizumab
Exclusion Criteria:
- Disease that can be treated with curative intent as assessed by patient's study
physician. If patient in this situation wishes for treatment with palliative intent
then they may enroll
- Multiple primary oropharyngeal (OP) tumors
- Primary cancer not originated from the oropharynx
- Has received any therapy for R/M disease. Therapy in the setting of curative intent
is allowed
- Patient is pregnant or breastfeeding
- Prior prophylactic or therapeutic vaccination with any human papillomavirus (HPV)
antigen except L1
* Note: previous receipt of the Gardasil (registered trademark) vaccine (including
Gardasil 9 [registered trademark]) or the Cervarix (registered trademark) vaccine
does not exclude
- Has received a live vaccine within 30 days prior to first dose of study treatment
- Examples of prohibited live vaccines include, but are not limited to measles,
mumps, rubella, varicella (chickenpox), zoster (shingles; Zostavax [registered
trademark] [not including Shingrix (registered trademark)]), yellow fever,
rabies, bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine
- Seasonal influenza vaccines for injection are generally killed virus vaccines
and are allowed; however, intranasal influenza vaccines (e.g., FluMist
[registered trademark] Quadrivalent) are live attenuated vaccines and are not
allowed. The three United States (US) FDA-approved coronavirus disease 2019
(COVID-19) vaccines (by Pfizer BioNTech, Moderna, and Janssen) and AstraZeneca
COVID-19 vaccine are based on messenger (m)RNA or replication-deficient
adenoviral vectors and are allowed
- Is currently participating in or, within 4 weeks prior to first dose of study
treatment, has participated in a study of an investigational agent or has used an
investigational device
- Note: Participants who have entered the follow-up phase of an investigational
study may participate as long as it has been 4 weeks after the last dose of the
previous investigational agent
- Patients with persistent toxicities of =< grade 3 (National Cancer Institute
[NCI]-Common Terminology Criteria for Adverse Events [CTCAE] v5.0) will be
excluded
- Diagnosis of immunodeficiency
- Known additional malignancy that is non-localized or progressing or has required
active treatment within the past 3 years prior to first dose of study treatment
* Note: Participants with usual basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, or carcinoma in situ (for example, in situ cervical cancer or
breast carcinoma, superficial bladder cancer, or non-invasive intraductal carcinoma
of the prostate) that have undergone potentially curative therapy are not excluded
- Radiographically detectable (even if asymptomatic and/or previously treated) central
nervous system metastases and/or carcinomatous meningitis as assessed by local site
investigator and radiology review
- Recipient of previous allogeneic tissue/solid organ transplant
- Known severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its
excipients
- History of myocarditis or pericarditis or other known clinically significant
underlying heart disease (e.g., cardiomyopathy, congestive heart failure,
symptomatic arrhythmia not controlled by medication, unstable angina, history of
acute myocardial infarction)
- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, sepsis, or psychiatric illness/social situations that would limit
compliance with study requirements
- Active or chronic infection with any of the following (with testing for all three
conditions required during screening for this study):
- Human immunodeficiency virus (HIV)
- Hepatitis C virus (HCV)
- Hepatitis B virus (HBV)
- Active autoimmune disease with immunodeficiency as a clinical component (e.g.,
rheumatoid arthritis, systemic lupus erythematosus [SLE], ulcerative colitis,
Crohn's disease, multiple sclerosis [MS], ankylosing spondylitis)
- Within 60 days prior to initiating first dose of protocol-indicated treatment,
patient has received therapy with immunosuppressive drugs such as cyclosporine,
adrenocorticotropic hormone (ACTH), alkylating agents, antimetabolites, radiation,
tumor necrosis factor (TNF) inhibitors, or systemic corticosteroids
- Recognized immunodeficiency diseases including cellular immunodeficiencies;
hypo-gammaglobulinemia or dys-gammaglobulinemia; or acquired, hereditary, or
congenital immunodeficiencies
- Patients and their close social, sexual, or domestic contacts may not have
non-healed wounds or active exfoliative skin conditions, such as eczema, burns,
impetigo, varicella-zoster virus infection, herpes simplex virus infection, severe
acne, severe diaper dermatitis with extensive areas of denuded skin, psoriasis,
lichen planus, or Darier disease (keratosis follicularis)
- History and presence of atopic dermatitis
- Patients and their close social, sexual, or domestic contacts may not have known
conditions associated with immunosuppression, such as HIV/acquired immunodeficiency
syndrome (AIDS), leukemia, lymphoma, generalized malignancy, solid organ transplant
recipient, or hematopoietic stem cell transplant recipient < 24 months
post-transplant OR >= 24 months, but who have graft-versus-host disease or disease
relapse, or be of less than 1 year of age
- Found at screening visit to have severe arrhythmias (e.g., atrial fibrillations),
sinus bradycardia (< 50 beats per minute [BPM]), sinus tachycardia (> 100 BPM) via
resting electrocardiography (EKG). Patients with controlled arrhythmias followed by
a cardiologist are eligible
- Patients with active interstitial lung disease (ILD)/pneumonitis or a history of
ILD/pneumonitis requiring treatment with systemic steroids. Hypoxemia (oxygen
saturation [SpO2] < 92% for 5 min or longer) by finger pulse oximetry corrected by
oxygen supplementation is allowed
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Vanderbilt University/Ingram Cancer Center
Address:
City:
Nashville
Zip:
37232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Vanderbilt-Ingram Service for Timely Access
Phone:
800-811-8480
Email:
cip@vumc.org
Investigator:
Last name:
Michael Gibson, MD, PhD
Email:
Principal Investigator
Start date:
May 16, 2023
Completion date:
September 30, 2028
Lead sponsor:
Agency:
Michael K. Gibson
Agency class:
Other
Source:
Vanderbilt-Ingram Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05799144
