Intratumoral Microdosing of Motolimod in HNSCC

NCT04272333 | Terminated Early Phase 1 FDA Drug

• 1 other identifier: PBI-CEL-01
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

HNSCC

Keywords

precision oncology; intratumoral microdosing; microdose injection; microdosing; in vivo oncology; in vivo drug sensitivity; tumor microenvironment; multiplexed immunohistochemistry; head and neck cancer; SCCHN; pharmacodynamic biomarkers; CIVO

Outcome Measures

Primary Outcomes (1)

• Quantification of Cell Death and Immune Cell Biomarkers by Immunohistochemistry (IHC) and In-Situ Hybridization (ISH) in Resected Tissue

  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 Outcomes (1)

• Number of Patients with Adverse Events

  Up to 28 days after microdose injection

Study Arms (1)

CIVO Microdose Injection of Motolimod and Nivolumab

EXPERIMENTAL

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; Biological: Nivolumab; Combination Product: Motolimod + Nivolumab

Interventions

Motolimod DRUG

Intratumoral microdose injection by the CIVO device.

Also known as: VTX2337

CIVO Microdose Injection of Motolimod and Nivolumab

Nivolumab BIOLOGICAL

Intratumoral microdose injection by the CIVO device.

Also known as: Opdivo

CIVO Microdose Injection of Motolimod and Nivolumab

Motolimod + Nivolumab COMBINATION_PRODUCT

Intratumoral microdose injection by the CIVO device.

CIVO Microdose Injection of Motolimod and Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability and willingness to comply with the study's visit and assessment schedule.
• Male or female ≥ 18 years of age at Visit 1 (Screening).
• Pathologic diagnosis of HNSCC.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• 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.

You may not qualify if:

• 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.
• Tumors near or involving critical structures for which, in the opinion of the treating clinician, injection would pose undue risk to the patient.
• Patients with a diagnosis of nasopharyngeal carcinoma.
• 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.
• 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.
• Patients with a history of concurrent second cancers requiring active, ongoing systemic treatment.
• Patients with active autoimmune diseases requiring treatment.
• 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.
• Patients that have received a live vaccine within 4 weeks of the baseline/screening visit.
• Use of any of the following ≤ 2 weeks prior to CIVO injection :
• 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.
• Biological response modifiers for treatment of active autoimmune disease.
• Hematopoietic growth factors.

Sponsors & Collaborators

• Presage Biosciences: lead
• Celgene: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (5)

University of California, San Francisco

San Francisco, California, 94158, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

Location

Portland VA

Portland, Oregon, 97239, United States

Location

Related Publications (5)

• Klinghoffer RA, Bahrami SB, Hatton BA, Frazier JP, Moreno-Gonzalez A, Strand AD, Kerwin WS, Casalini JR, Thirstrup DJ, You S, Morris SM, Watts KL, Veiseh M, Grenley MO, Tretyak I, Dey J, Carleton M, Beirne E, Pedro KD, Ditzler SH, Girard EJ, Deckwerth TL, Bertout JA, Meleo KA, Filvaroff EH, Chopra R, Press OW, Olson JM. A technology platform to assess multiple cancer agents simultaneously within a patient's tumor. Sci Transl Med. 2015 Apr 22;7(284):284ra58. doi: 10.1126/scitranslmed.aaa7489.

  PMID: 25904742 BACKGROUND

• Frazier JP, Bertout JA, Kerwin WS, Moreno-Gonzalez A, Casalini JR, Grenley MO, Beirne E, Watts KL, Keener A, Thirstrup DJ, Tretyak I, Ditzler SH, Tripp CD, Choy K, Gillings S, Breit MN, Meleo KA, Rizzo V, Herrera CL, Perry JA, Amaravadi RK, Olson JM, Klinghoffer RA. Multidrug Analyses in Patients Distinguish Efficacious Cancer Agents Based on Both Tumor Cell Killing and Immunomodulation. Cancer Res. 2017 Jun 1;77(11):2869-2880. doi: 10.1158/0008-5472.CAN-17-0084. Epub 2017 Mar 31.

  PMID: 28364003 BACKGROUND

• Dey J, Kerwin WS, Grenley MO, Casalini JR, Tretyak I, Ditzler SH, Thirstrup DJ, Frazier JP, Pierce DW, Carleton M, Klinghoffer RA. A Platform for Rapid, Quantitative Assessment of Multiple Drug Combinations Simultaneously in Solid Tumors In Vivo. PLoS One. 2016 Jun 30;11(6):e0158617. doi: 10.1371/journal.pone.0158617. eCollection 2016.

  PMID: 27359113 BACKGROUND

• Moreno-Gonzalez A, Olson JM, Klinghoffer RA. Predicting responses to chemotherapy in the context that matters - the patient. Mol Cell Oncol. 2015 Jun 10;3(1):e1057315. doi: 10.1080/23723556.2015.1057315. eCollection 2016 Jan.

  PMID: 27308571 BACKGROUND

• Gundle KR, Deutsch GB, Goodman HJ, Pollack SM, Thompson MJ, Davis JL, Lee MY, Ramirez DC, Kerwin W, Bertout JA, Grenley MO, Sottero KHW, Beirne E, Frazier J, Dey J, Ellison M, Klinghoffer RA, Maki RG. Multiplexed Evaluation of Microdosed Antineoplastic Agents In Situ in the Tumor Microenvironment of Patients with Soft Tissue Sarcoma. Clin Cancer Res. 2020 Aug 1;26(15):3958-3968. doi: 10.1158/1078-0432.CCR-20-0614. Epub 2020 Apr 16.

  PMID: 32299817 BACKGROUND

Related Links

• Presage Website

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Interventions

VTX-2337; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Medical Director

  Presage Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: February 17, 2020
• Study Start: October 15, 2021
• Primary Completion: March 25, 2022
• Study Completion: March 25, 2022
• Last Updated: April 14, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)