Trial Title:
PBI-MST-01 (NCT04541108) Substudy AZN-05: Intratumoral Microdosing of Rilvegostomig, Volrustomig, and Sabestomig in HNSCC
NCT ID:
NCT06366451
Condition:
Head and Neck Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Pembrolizumab
Conditions: Keywords:
HNSCC
intratumoral microdosing
microdose injection
microdosing
in vivo oncology
tumor microenvironment
multiplexed immunohistochemistry
head and neck cancer
head and neck squamous cell carcinoma
pharmacodynamic biomarkers
CIVO
master protocol
precision oncology
spatial biology
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
This is an exploratory clinical trial to evaluate intratumoral mechanistic effects of
novel and approved agents on intact human tumors. This is a cohort substudy of a Master
Protocol (PBI-MST-01, NCT04541108) framework, under which comparisons will not be made
between substudy cohorts.
Primary purpose:
Basic Science
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Rilvegostomig
Description:
Intratumoral microdose injection by the CIVO device.
Arm group label:
Rilvegostomig, Volrustomig, Sabestomig, Pembrolizumab
Other name:
AZD2936
Intervention type:
Biological
Intervention name:
Volrustomig
Description:
Intratumoral microdose injection by the CIVO device.
Arm group label:
Rilvegostomig, Volrustomig, Sabestomig, Pembrolizumab
Other name:
MEDI5752
Intervention type:
Biological
Intervention name:
Sabestomig
Description:
Intratumoral microdose injection by the CIVO device.
Arm group label:
Rilvegostomig, Volrustomig, Sabestomig, Pembrolizumab
Other name:
AZD7789
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Intratumoral microdose injection by the CIVO device.
Arm group label:
Rilvegostomig, Volrustomig, Sabestomig, Pembrolizumab
Other name:
Keytruda, MK-3475
Summary:
This is a multi-center, open-label, Phase 0 substudy designed to evaluate the localized
pharmacodynamics (PD) of rilvegostomig, volrustomig, and sabestomig within the tumor
microenvironment (TME) when administered intratumorally in microdose quantities via the
CIVO device in patients presenting with Head and Neck Squamous Cell Carcinoma (HNSCC)
with a surface accessible lesion, who are scheduled for tumor and/or regional node
dissection as part of their standard treatment. PD effects due to injected
investigational agents will be compared to those elicited by pembrolizumab alone, which
will also be injected in microdose quantities via the CIVO device.
Detailed description:
The CIVO Microdose Injection Device (MID) simultaneously delivers multiple drugs and drug
combinations (Up to 8), each in microdose amounts, into a single patient tumor and
enables comparisons of the resulting biomarker responses that occurred while that tumor
was still in the native microenvironment. AstraZeneca is developing three novel assets:
rilvegostomig, volrustomig, and sabestomig, all of which are bispecific monoclonal
antibodies designed to stimulate antitumor immunity. In this Phase 0 clinical trial, the
PD effects of these investigational assets in the TME of patients presenting with HNSCC
will be evaluated. These investigational assets will be injected alone in microdose
quantities at tumor sites in HNSCC patients. Pembrolizumab, also used therapeutically in
this patient population, will be included in the CIVO injection array administered as a
single agent. The CIVO-injected portion of the tissue will be analyzed for localized
response at sites of drug exposure in the TME.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Ability and willingness to provide written informed consent. Voluntary written
consent must be given before performance of any study related procedure not part of
standard medical care, with the understanding that consent may be withdrawn by the
patient at any time without prejudice to future medical care.
2. Male or female ≥ 18 years of age at Visit 1 (Screening).
3. Pathologic diagnosis of Head and Neck Squamous Cell Carcinoma (HNSCC) of the
oropharynx, hypopharynx, oral cavity, or larynx.
4. Ability and willingness to comply with the study's visits and assessment schedule.
5. At least one lesion (primary tumor, recurrent tumor, metastasis, or metastatic lymph
node) that is surface accessible for CIVO injection that contains viable minimum
tumor tissue volume and characteristics (e.g., based on clinical evaluation,
available pre-operative imaging, pre-injection ultrasound imaging, or pathology
reports indicating lesion with appropriate viable tumor volume without excessive
cysts or necrosis) and for which there is a planned surgical intervention. The
patient's presentation, surgical and pathology plan may determine whether a lesion
is eligible with respect to a given CIVO MID needle configuration.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
7. Female patients who:
- Are postmenopausal for at least one year before the screening visit, OR
- Are surgically sterile, OR
- Are of childbearing potential who agree to practice a highly effective method
of contraception from the time of signing the Informed Consent Form (ICF) until
150 days after the CIVO injection OR agree to completely abstain from
heterosexual intercourse.
- Agree to refrain from donating, or retrieving for their own use, ova until 150
days after the CIVO injection.
- Agree to refrain from breastfeeding until 150 days after the CIVO injection.
8. Male patients, even if surgically sterile (i.e., status post-vasectomy), who:
- Agree to practice effective barrier contraception from the time of signing the
ICF until 150 days after the CIVO injection OR agree to completely abstain from
heterosexual intercourse.
- Agree to refrain from fathering a child or donating sperm until 150 days after
the CIVO injection.
Exclusion Criteria:
1. Tumors and/or effaced nodes that are anticipated by the Investigator to lack a
sufficient volume of viable tumor tissue (Based on available pre-operative imaging,
pre-injection ultrasound imaging, or pathology reports) for CIVO microdose injection
due to necrosis, cysts, excessive stroma, fibrosis, or treatment-induced tissue
changes.
2. Tumors near or involving critical structures for which, in the opinion of the
treating clinician, injection would pose undue risk to the patient.
3. Prior exposure to immune-mediated therapy including, but not limited to, other
anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies within the last 5
years.
4. Patients with concurrent cancer, immune disease or active infection requiring
systemic or radiotherapy.
5. Female patients who:
- Intend to become pregnant during the study,
- Are both lactating and breastfeeding, OR
- Have a positive beta-subunit human chorionic gonadotropin (beta-hCG) pregnancy
test at screening verified by the Investigator.
6. Any uncontrolled intercurrent illness, condition, serious medical or psychiatric
illness, or circumstance that, in the opinion of the Investigator, could interfere
with adherence to the study's procedures or requirements, or otherwise compromise
the study's objectives.
7. History of organ transplant.
8. Major surgery within 4 weeks prior to injection: subject must have adequate wound
healing and have recovered from any prior surgery.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UC Davis
Address:
City:
Sacramento
Zip:
95817
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Research Supervisor
Investigator:
Last name:
Arnaud Bewley, MD
Email:
Principal Investigator
Facility:
Name:
LSU Health Sciences Center - Shreveport
Address:
City:
Shreveport
Zip:
71115
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Research Coordinator
Facility:
Name:
Montefiore Medical Center
Address:
City:
Bronx
Zip:
10467
Country:
United States
Status:
Recruiting
Contact:
Last name:
Research Coordinator
Facility:
Name:
University of North Carolina
Address:
City:
Chapel Hill
Zip:
27599
Country:
United States
Status:
Recruiting
Contact:
Last name:
Research Coordinator
Facility:
Name:
Oregon Health & Science University (OHSU)
Address:
City:
Portland
Zip:
97239
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Research Coordinator
Facility:
Name:
University of Pennsylvania
Address:
City:
Philadelphia
Zip:
19107
Country:
United States
Status:
Recruiting
Contact:
Last name:
Research Coordinator
Facility:
Name:
Sarah Cannon Medical Center
Address:
City:
Charleston
Zip:
29406
Country:
United States
Status:
Recruiting
Contact:
Last name:
Research Coordinator
Start date:
May 22, 2024
Completion date:
March 2025
Lead sponsor:
Agency:
Presage Biosciences
Agency class:
Industry
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Source:
Presage Biosciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06366451
