Clinical Trials /

Intratumoral Microdosing of Motolimod in HNSCC



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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:



Early Phase 1

Trial Eligibility



  • Brief Title: Intratumoral Microdosing of Motolimod in HNSCC
  • Official Title: 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

Clinical Trial IDs

  • NCT ID: NCT04272333




MotolimodVTX2337CIVO Microdose Injection of Motolimod and Nivolumab
NivolumabOpdivoCIVO Microdose Injection of Motolimod and Nivolumab


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.

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.

Trial Arms

CIVO Microdose Injection of Motolimod and NivolumabExperimentalPatients 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.
  • Motolimod
  • Nivolumab

Eligibility 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 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

         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.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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).

Secondary Outcome Measures

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


Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Presage Biosciences

Trial Keywords

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

Last Updated

May 13, 2021