Phase 0 Master Protocol for CIVO Intratumoral Microdosing of Anti-Cancer Therapies

April 15, 2024 updated by: Presage Biosciences

A Phase 0 Master Protocol Using the CIVO® Platform to Evaluate Intratumoral Microdoses of Anti-Cancer Therapies in Patients With Solid Tumors

This is a multi-center, open-label Phase 0 Master Protocol designed to study the localized pharmacodynamics (PD) of anti-cancer therapies within the tumor microenvironment (TME) when administered intratumorally in microdose quantities via the CIVO device in patients with surface accessible solid tumors for which there is a scheduled surgical intervention. CIVO stands for Comparative In Vivo Oncology. Multiple substudies will include specified investigational agents and combinations to be evaluated.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

CIVO is a research tool composed of a hand-held single-use sterile injector coupled with fluorescent tracking microspheres called CIVO GLO that mark the sites of drug microdose injection, enabling rapid assessment of multiple oncology drugs or drug combinations simultaneously within a patient's tumor. Tumor responses to cancer treatments are highly context-specific and often involve complex interactions between the anti-cancer therapy, genetically diverse tumor cells, and a heterogeneous TME. This complexity is rarely modeled accurately in preclinical translational models of cancer. By utilizing intratumoral microdose injections with CIVO in advance of scheduled surgical intervention, this study will evaluate anti-cancer therapies directly in patients each with their own unique tumor genomic profile, intact TME, and immune system functional status. Because the platform delivers microdose amounts of each test agent or combination directly into the patient's tumor tissue, hypotheses can be tested earlier in the drug development process, consistent with the goals of the 2006 FDA Exploratory IND Guidance for Industry.

The CIVO device penetrates solid tumors and simultaneously delivers subtherapeutic microdoses of up to eight anti-cancer agents or combinations of anti-cancer agents co-injected with CIVO GLO into discrete regions of the tumor as drug columns. At the time of the planned surgical intervention (at least four hours to up to seven days after the CIVO microdose injection), the injected tumor tissue is then excised and tumor responses are assessed via histological staining of tumor cross-sections sampled perpendicular to each injection column. Co-injection with CIVO GLO enables identification of each injection site during resection as well as in tissues stained for analysis. This Phase 0 Master Protocol is aimed at distinguishing promising candidates earlier in the drug development process while also avoiding systemic toxicities associated with typical clinical exposures to these therapies.

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • 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 Locations

  • United States
    • California
      • Sacramento, California, United States, 95817
        • Recruiting
        • UC Davis
        • Principal Investigator:
          • Arnaud Bewley, MD
        • Contact:
          • Randev Clinical Research Supervisor
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Recruiting
        • Emory Winship Cancer Institute
        • Contact:
          • Allyson Anderson
        • Principal Investigator:
          • Mihir Patel, MD
        • Sub-Investigator:
          • Ken Cardona, MD
    • Louisiana
      • Shreveport, Louisiana, United States, 71115
        • Recruiting
        • LSU Health Sciences Center - Shreveport
        • Contact:
          • Research Coordinator
    • 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
        • Principal Investigator:
          • Sid Sheth, MD
      • Winston-Salem, North Carolina, United States, 27157
        • Withdrawn
        • Wake Forest University Health Sciences
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Completed
        • UC Health
    • Oregon
      • Portland, Oregon, United States, 97239
        • 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, 29406
        • Recruiting
        • Sarah Cannon Research Institute
        • Contact:
          • Research Coordinator
        • Principal Investigator:
          • Jeffrey Houlton, MD
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • UT Health
        • Contact:
          • Research Coordinator
        • Principal Investigator:
          • Ernest Conrad, MD
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • University of Washington
        • Contact:
          • Roxanne Moore
        • Principal Investigator:
          • Elyse Brinkmann, MD

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

*This list is representative of study inclusion/exclusion criteria. Each substudy may include variations on these criteria.

Inclusion Criteria:

  1. Ability and willingness to comply with the study's visit and assessment schedule.
  2. Male or female ≥ 18 years of age at Visit 1 (Screening).
  3. Pathologic diagnosis of [solid tumors] indicated in the relevant substudy(ies).
  4. 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.
  5. At least one lesion (primary tumor, recurrent tumor, 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. 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) and during study participation OR agree to completely abstain from heterosexual intercourse.
    • Agree to refrain from donating ova during study participation.

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 and during study participation OR agree to completely abstain from heterosexual intercourse.
  • Agree to refrain from donating sperm during study participation.

Exclusion Criteria:

  1. Tumors near or involving critical structures for which, in the opinion of the treating clinician, injection would pose undue risk to the patient.

  2. Female patients who are:

    • Both lactating and breastfeeding, OR
    • Have a positive β-subunit human chorionic gonadotropin (β-hCG) pregnancy test at screening verified by the Investigator.
  3. 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.

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
Intervention / Treatment
Experimental: Rilvegostomig, Volrustomig, Sabestomig, 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, and pembrolizumab alone.
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantification of Selected Pharmacodynamic Biomarkers as Specified in Substudies by IHC, ISH, and/or Spatial Biology Platforms
Time Frame: 4 hours-7 days after microdose injection
Quantification of biomarker-positive and biomarker-negative cells will be performed within the tumor microenvironment around each of the injection sites in each resected patient sample by IHC, ISH, or spatial biology platforms. An aggregate analysis of this quantification may be done across patient samples in each substudy to evaluate trends in tumor response. The biomarkers evaluated may include, but are not limited to biomarkers for cell death (e.g. cleaved caspase 3), T-cells (e.g. CD3, CD8/Granzyme B, CD4), natural killer (NK)/myeloid cells (e.g. CD56/Granzyme B, CD86, CD68, CD163), and proinflammatory cytokines (e.g., interferon gamma, tumor necrosis factor alpha, interferon gamma-induced protein 10).
4 hours-7 days after microdose injection

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients with Adverse Events
Time Frame: Up to 28 days after microdose injection
Relationship of AE to study drug(s) or CIVO device will be determined using an AE Relatedness Grading System.
Up to 28 days after microdose injection

Collaborators and Investigators

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

Sponsor

Presage Biosciences

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • 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)

July 26, 2021

Primary Completion (Estimated)

December 1, 2031

Study Completion (Estimated)

December 1, 2031

Study Registration Dates

First Submitted

September 1, 2020

First Submitted That Met QC Criteria

September 1, 2020

First Posted (Actual)

September 9, 2020

Study Record Updates

Last Update Posted (Actual)

April 18, 2024

Last Update Submitted That Met QC Criteria

April 15, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PBI-MST-01 (Presage Biosciences)
  • MST01-MSD-03 (Other Identifier: Presage Biosciences)
  • MST01-TAK-02 (NCT06062602) (Other Identifier: Presage Biosciences)
  • MST01-AZN-05 (NCT06366451) (Other Identifier: 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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