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A Study to Evaluate Immune Biomarker Modulation in Response to VTX-2337 in Combination With an Anti- PD-1 Inhibitor in Head and Neck Cancer

NCT03906526

Description:

This is an open label, Phase 1b pre-operative window of opportunity biomarker trial to analyze the combination of intravenous (IV) anti-PD-1 inhibitor, nivolumab, given along with toll-like receptor 8 (TLR 8) agonist motolimod delivered either subcutaneously (SC) or by intratumoral injection (IT) in subjects with squamous cell carcinoma of the head and neck (SCCHN). Subjects with previously untreated, resectable SCCHN, will be recruited onto this trial and will initially undergo pre-treatment diagnostic imaging and biological sample collection. These subjects will undergo pre-operative study treatment for a 3 to 4-week period prior to a scheduled surgical resection.

Related Conditions:
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate Immune Biomarker Modulation in Response to VTX-2337 in Combination With an Anti- PD-1 Inhibitor in Head and Neck Cancer
  • Official Title: A Phase 1b Multicenter Pre-Surgical Study to Evaluate Immune Biomarker Modulation in Response to Motolimod (VTX-2337) in Combination With Nivolumab in Subjects With Resectable Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Clinical Trial IDs

  • ORG STUDY ID: VTX-2337-HN-001
  • SECONDARY ID: U1111-1223-3488
  • NCT ID: NCT03906526

Conditions

  • Carcinoma, Squamous Cell

Interventions

DrugSynonymsArms
VTX-2337VTX-378Combination Arm 3: Nivolumab and Motolimod
NivolumabOpdivoCombination Arm 3: Nivolumab and Motolimod

Purpose

This is an open label, Phase 1b pre-operative window of opportunity biomarker trial to analyze the combination of intravenous (IV) anti-PD-1 inhibitor, nivolumab, given along with toll-like receptor 8 (TLR 8) agonist motolimod delivered either subcutaneously (SC) or by intratumoral injection (IT) in subjects with squamous cell carcinoma of the head and neck (SCCHN). Subjects with previously untreated, resectable SCCHN, will be recruited onto this trial and will initially undergo pre-treatment diagnostic imaging and biological sample collection. These subjects will undergo pre-operative study treatment for a 3 to 4-week period prior to a scheduled surgical resection.

Trial Arms

NameTypeDescriptionInterventions
Monotherapy Arm 1: NivolumabExperimentalNivolumab IV every 2 weeks
  • Nivolumab
Monotherapy Arm 2: MotolimodExperimentalMotolimod IT injection weekly
  • VTX-2337
Combination Arm 3: Nivolumab and MotolimodExperimentalNivolumab IV every 2 weeks and Motolimod IT injection weekly
  • VTX-2337
  • Nivolumab
Combination Arm 4: Nivolumab and MotolimodExperimentalNivolumab IV every 2 weeks and Motolimod SC injection weekly
  • VTX-2337
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).

          -  Subject has Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.

          -  Subject has a new clinical or pathologic diagnosis of resectable HPV+ or HPV- SCCHN of
             the oral cavity, pharynx, or larynx

          -  Macroscopic complete resection of the primary tumor must be planned and subjects
             should have no medical contraindication to surgery.

          -  Subject consents to and has tumor accessible for tumor biopsy pre-treatment.

          -  Subjects must have acceptable hematopoietic, liver, renal, and coagulation function as
             assessed by laboratory tests.

        Exclusion Criteria:

          -  Subject has any significant medical condition, laboratory abnormality, or psychiatric
             illness that would prevent the subject from participating in the study

          -  Subject has unresectable or inoperable tumors

          -  Subject has primary tumors of the sinuses, paranasal sinuses, or nasopharynx, or
             unknown primary tumors

          -  Subject has evidence of distant metastasis

          -  Subject is a pregnant or nursing female.

          -  Subject has active or uncontrolled infection including known HIV infection or known
             chronic hepatitis B or C.

          -  Subject has active autoimmune disease.

          -  Subject has clinically significant ophthalmologic disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Numbers of CD8+ T cells within the tumor pre-treatment and post-surgery
Time Frame:Screening through Study Day 52
Safety Issue:
Description:Tumor immune modulation will be evaluated by counting the number of tumor infiltration CD8+ T cells before and after treatment.

Secondary Outcome Measures

Measure:Number of Patients With adverse events that lead to delay in resection
Time Frame:Screening through Study Day 52
Safety Issue:
Description:Study will evaluate the number of patients who experience adverse events that lead to a significant delay in surgical resection.
Measure:Evaluation of safety and tolerability of nivolumab, motolimod and the combination of nivolumab with motolimod
Time Frame:Up to approximately 112 days
Safety Issue:
Description:Subject will be monitored for AEs both during treatment and for a specified period after last dose of study treatment. AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Motolimod
  • Nivolumab
  • Head and Neck Cancer
  • Squamous Cell Carcinoma
  • Checkpoint inhibitor
  • anti-PD1 inhibitor
  • TLR 8 agonist

Last Updated

September 27, 2019