PBI-MST-01 (NCT04541108) Substudy AZN-05: Intratumoral Microdosing of Rilvegostomig, Volrustomig, Sabestomig, and AZD9592 in HNSCC

January 16, 2025 updated by: Presage Biosciences

A Phase 0 Multicenter Study of the Pharmacodynamic Effects of Intratumoral Microdose Administration of Rilvegostomig, Volrustomig, Sabestomig, and AZD9592

This is a multi-center, open-label, Phase 0 substudy designed to evaluate the localized pharmacodynamics (PD) of rilvegostomig, volrustomig, sabestomig, and AZD9592 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, either as single agents or as AZD9592 drug combinations with the evaluated biologics, will be compared to those elicited by pembrolizumab alone, which will also be injected in microdose quantities via the CIVO device.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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. In addition, microdoses of AZD9592, a novel antibody drug conjugate (ADC), alone or in combinations with the evaluated biologics will also be assessed. The CIVO-injected portion of the tissue will be analyzed for localized response at sites of drug exposure in the TME.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • California
      • Sacramento, California, United States, 95817
        • Recruiting
        • UC Davis
        • Principal Investigator:
          • Arnaud Bewley, MD
        • Contact:
          • Clinical Research Supervisor
    • New York
      • Bronx, New York, United States, 10467
        • Recruiting
        • Montefiore Medical Center
        • Contact:
          • Research Coordinator
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina
        • Contact:
          • Research Coordinator
    • Oregon
      • Portland, Oregon, United States, 97239
        • Not yet recruiting
        • Oregon Health & Science University (OHSU)
        • Contact:
          • Research Coordinator
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • University of Pennsylvania
        • Contact:
          • Research Coordinator
    • South Carolina
      • Charleston, South Carolina, United States, 29407
        • Recruiting
        • Medical University of South Carolina
        • Contact:
          • Research Coordinator
      • Charleston, South Carolina, United States, 29406
        • Recruiting
        • Sarah Cannon Medical Center
        • Contact:
          • Research Coordinator

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 7 months 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 7 months after the CIVO injection.
    • Agree to refrain from breastfeeding until 7 months 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 7 months after the CIVO injection OR agree to completely abstain from heterosexual intercourse.
    • Agree to refrain from fathering a child or donating sperm until 7 months 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. Previous treatment with another ADC containing a chemotherapeutic agent that inhibits topoisomerase 1 activity or with another epidermal growth factor receptor (EGFR) and/or mesenchymal-epithelial transition factor (c-MET) targeted ADC.
  5. Patients with concurrent cancer, immune disease or active infection requiring systemic or radiotherapy.

  6. 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.
  7. 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.
  8. History of organ transplant.
  9. Major surgery within 4 weeks prior to injection: subject must have adequate wound healing and have recovered from any prior surgery.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Rilvegostomig, Volrustomig, Sabestomig, AZD9592, Pembrolizumab
HNSCC patients presenting with a surface accessible lesion who are scheduled for tumor and/or regional node dissection as part of their standard treatment will be injected one to three days prior to surgery using the CIVO device. The planned injection scheme includes: vehicle control and microdoses of rilvegostomig, volrustomig, sabestomig, AZD9592, and pembrolizumab as single agents and AZD9592 drug combinations with the evaluated biologics.
Biological: Pembrolizumab
Intratumoral microdose injection by the CIVO device.
Other Names:
  • Keytruda, MK-3475
Biological: Rilvegostomig
Intratumoral microdose injection by the CIVO device.
Other Names:
  • AZD2936
Biological: Volrustomig
Intratumoral microdose injection by the CIVO device.
Other Names:
  • MEDI5752
Biological: Sabestomig
Intratumoral microdose injection by the CIVO device.
Other Names:
  • AZD7789
Biological: AZD9592
Intratumoral microdose injection by the CIVO device.
Combination product: AZD9592 + Rilvegostomig
Intratumoral microdose injection by the CIVO device.
Combination product: AZD9592 + Volrustomig
Intratumoral microdose injection by the CIVO device.
Combination product: AZD9592 + Sabestomig
Intratumoral microdose injection by the CIVO device.
Combination product: AZD9592 + Pembrolizumab
Intratumoral microdose injection by the CIVO device.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Evaluation of signature scores using Gene Set Variability Analysis within regions injected with microdoses of rilvegostomig, volrustomig, sabestomig, AZD9592, or pembrolizumab as single agents or as AZD9592 drug combinations with the evaluated biologics
Time Frame: 1 to 3 days after microdose injection
The localized activity of injected microdoses will be analyzed using the NanoString GeoMx Digital Spatial Profiler (DSP) and the GeoMx Cancer Transcriptome Atlas to comprehensively profile over 1800 genes simultaneously with spatial resolution to describe tumor biology, the TME, and the immune response signatures of each drug at an injection site. DSP outcomes may be validated via IHC, immunofluorescence, or ISH technique.
1 to 3 days after microdose injection

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of reported Adverse Events and/or Adverse Device Effects [Safety and Tolerability]
Time Frame: Up to 28 days after microdose injection
Safety of the microdose injection procedure and injected content will be assessed by quantification of the frequency, intensity, and relatedness of all reported Adverse Events and/or Adverse Device Effects.
Up to 28 days after microdose injection

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Evaluation of tumor whole exome sequencing (WES)/whole transcriptome sequencing (WTS)
Time Frame: Sample collected at screening
Tumor WES/WTS will be performed to help develop a comprehensive understanding of the observed PD responses of the tumor samples to the injected microdoses of the study drugs. Tumor WES/WTS (with matched blood circulating tumor DNA as control) will collect information on the tumor and TME background to provide critical tumor- and immune-related information such as, but not limited to, T-cell and B-cell repertoire, microsatellite instability, tumor mutational burden, and immunogenomic changes/immune profiling of the TME.
Sample collected at screening

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Presage Biosciences

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
AstraZeneca

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Study Director, Presage Biosciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 22, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 3, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 11, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 16, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 16, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MST01-AZN-05
  • PBI-MST-01 (Presage Biosciences)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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