Intratumoral Microdosing of Motolimod in HNSCC

April 6, 2022 updated by: Presage Biosciences

A Phase 0 Study Using the CIVO® Platform to Evaluate Intratumoral Microdoses of Motolimod Singly and in Combination With Nivolumab in Patients With Head and Neck Cancer

This is a multi-center, single arm, open-label, multi-agent, localized pharmacodynamic biomarker Phase 0 trial designed to study the biological effects within the tumor microenvironment of motolimod and motolimod combined with nivolumab when administered intratumorally in microdose quantities via the CIVO device in patients with head and neck squamous cell carcinoma (HNSCC). CIVO stands for comparative in vivo oncology.

Study Overview

Status

Terminated

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. In this Phase 0 intratumoral microdosing study in human patients with pathologic diagnosis of HNSCC with at least one lesion (primary, recurrent, or effaced metastatic lymph nodes) for which there is a planned surgical intervention, we will evaluate motolimod's ability to activate immune effector cells within the local tumor microenvironment. Additionally, this study will examine motolimod in combination with nivolumab to study whether motolimod enhances the localized immune responses compared to those of either immunotherapy alone. Motolimod singly and in combination with nivolumab will be delivered intratumorally in subtherapeutic microdose quantities via CIVO.

The CIVO device penetrates solid tumors and 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. At the time of the planned surgical intervention (at least four hours to up to four 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. 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.

Study Type

Interventional

Enrollment (Actual)

1

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 Locations

  • United States
    • California
      • San Francisco, California, United States, 94158
        • University of California, San Francisco
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Baptist Health
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University (OHSU)
      • Portland, Oregon, United States, 97239
        • Portland VA

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

Genders Eligible for Study

All

Description

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 HNSCC.
  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 or recurrent tumor) ≥ 2 cm in the shortest diameter that is accessible for ultrasound-guided percutaneous CIVO injection and for which there is a planned surgical intervention. An effaced metastatic lymph node may only be selected with prior Sponsor approval. Treatment plan may include adjuvant radiation or chemotherapy, and subjects should have no medical contraindication to surgery.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

  7. Female patients who :

    • Are postmenopausal for at least 24 consecutive months (i.e., have not had menses at any time during the preceding 24 consecutive months), OR
    • Are surgically sterile, OR
    • Are of childbearing potential (FCBP) who agree to true abstinence from heterosexual intercourse (which must be source documented) or to use a highly effective contraceptive method (e.g., combined [containing estrogen and progestogen] or progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, intravaginal, patch, or implantable]; bilateral tubal ligation; intrauterine device; intrauterine hormone-releasing system; or vasectomized partner sterilization [note that vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the FCBP trial participant and that the vasectomized partner has received medical assessment of the surgical success]) from the time of signing the Informed Consent Form (ICF) and during study participation.
    • Agree to refrain from donating ova during study participation.

Male patients who:

  • Agree to practice true abstinence from heterosexual intercourse or agree to use a condom (a latex condom is recommended) during sexual contact with a pregnant female or a FCBP from the time of signing the ICF and while participating in the study, even if he has undergone a successful vasectomy.
  • Agree to refrain from donating sperm during study participation.

Exclusion Criteria:

  1. Tumors 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 injection due to size, location, necrosis, cysts, excessive stroma, fibrosis, or treatment-induced tissue changes. Lesions that have received neoadjuvant radiation therapy may lack sufficient viable tumor tissue for CIVO injection procedures.
  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. Patients with a diagnosis of nasopharyngeal carcinoma.

  4. Female patients who are:

    • Both lactating and breastfeeding, OR
    • Have a positive urine β-subunit of human chorionic gonadotropin (β-hCG) pregnancy test at screening verified by the Investigator.
  5. 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.
  6. Patients with a history of concurrent second cancers requiring active, ongoing systemic treatment.
  7. Patients with active autoimmune diseases requiring treatment.
  8. Patients with known human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) with uncontrolled viral load and CD4 less than 200, or known chronic hepatitis B/C.
  9. Patients that have received a live vaccine within 4 weeks of the baseline/screening visit.

  10. Use of any of the following ≤ 2 weeks prior to CIVO injection :

    1. Chronic systemic immunosuppressive therapy or corticosteroids (e.g., prednisone or equivalent exceeding a total dose of 140 mg over the last 14 days). Intranasal, inhaled, topical, or local corticosteroid injections (e.g., intra-articular injection), or steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication) are exceptions to this criterion.
    2. Biological response modifiers for treatment of active autoimmune disease.
    3. Hematopoietic growth factors.
    4. Anticoagulants such as warfarin or low-molecular-weight heparin.

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: CIVO Microdose Injection of Motolimod and Nivolumab
Patients who are scheduled for surgical biopsy or tumor resection surgery will be injected at least four hours to up to four days prior to surgery using the CIVO device. Each needle of the CIVO device will deliver up to 8.3 microliters of solution, including a vehicle control (sterile saline) or subtherapeutic microdoses of motolimod, nivolumab, or motolimod combined with nivolumab. Each microdose is simultaneously injected in a columnar fashion through each of 8, 5, or 3 needles (in a device configuration determined by tumor dimensions) into a single solid tumor or effaced metastatic lymph node.
Drug: Motolimod
Intratumoral microdose injection by the CIVO device.
Other Names:
  • VTX2337
Biological: Nivolumab
Intratumoral microdose injection by the CIVO device.
Other Names:
  • Opdivo
Combination product: Motolimod + Nivolumab
Intratumoral microdose injection by the CIVO device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantification of Cell Death and Immune Cell Biomarkers by Immunohistochemistry (IHC) and In-Situ Hybridization (ISH) in Resected Tissue
Time Frame: 4 hours-4 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 of each resected patient sample by IHC and ISH. An aggregate analysis of this quantification may be done across patient samples to evaluate trends in tumor response. List of biomarkers evaluated may include biomarkers for cell death (e.g. cleaved caspase 3), T-cells (e.g. CD3, CD8/Granzyme B), and natural killer (NK)/myeloid cells (e.g. CD56/Granzyme B, CD86, CD68, CD163).
4 hours-4 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 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

Bristol-Myers Squibb
Celgene

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

Helpful Links

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)

October 15, 2021

Primary Completion (ACTUAL)

March 25, 2022

Study Completion (ACTUAL)

March 25, 2022

Study Registration Dates

First Submitted

February 10, 2020

First Submitted That Met QC Criteria

February 12, 2020

First Posted (ACTUAL)

February 17, 2020

Study Record Updates

Last Update Posted (ACTUAL)

April 14, 2022

Last Update Submitted That Met QC Criteria

April 6, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PBI-CEL-01

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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