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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 tislelizumab given along with motolimod delivered either subcutaneously or by intratumoral injection in subjects with resectable HPV+/- squamous cell carcinoma of the head and neck.

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

Not yet 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 Tislelizumab (BGB-A317) in Subjects With 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
A317BGB-A317Monotherapy Arm 1: Tislelizumab
VTX-2337VTX-378Monotherapy Arm 2: Motolimod

Purpose

This is an open label, Phase 1b pre-operative window of opportunity biomarker trial to analyze the combination of intravenous tislelizumab given along with motolimod delivered either subcutaneously or by intratumoral injection in subjects with resectable HPV+/- squamous cell carcinoma of the head and neck.

Detailed Description

      This is an open-label, Phase 1b biomarker trial to analyze the combination of an anti-PD-1
      inhibitor, tislelizumab, given along with toll-like receptor 8 (TLR 8) agonist, motolimod, in
      subjects with resectable, HPV-positive or HPV-negative, SCCHN. Subjects with previously
      untreated, resectable SCCHN, with no prior history of SCCHN, will be recruited onto this
      trial and will initially undergo pre-treatment diagnostic biopsy, tumor imaging by computed
      tomography (CT) or magnetic resonance imaging (MRI) scan and peripheral blood collection.
      These subjects will undergo pre-operative study treatment for a 3 to 4-week period prior to
      their scheduled surgical resection
    

Trial Arms

NameTypeDescriptionInterventions
Monotherapy Arm 1: TislelizumabExperimentalTislelizumab IV (1 infusion every 3 weeks)
  • A317
Monotherapy Arm 2: MotolimodExperimentalMotolimod IT injection (1 injection every week)
  • VTX-2337
Combination Arm 3: Tislelizumab and MotolimodExperimentalTislelizumab IV (1 infusion every 3 weeks) and motolimod IT injection (1 injection every week)
  • A317
  • VTX-2337
Combination Arm 4: Tislelizumab and MotolimodExperimentalTislelizumab IV (1 infusion every 3 weeks) and motolimod SC injection (1 injection every week)
  • A317
  • VTX-2337

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.

          -  Females of childbearing potential (FCBP) and males must: Either commit to true
             abstinence from heterosexual intercourse or to use a highly effective contraceptive
             method

          -  Have negative pregnancy test

          -  Subjects must have the following laboratory values:

               -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

               -  Hemoglobin (Hgb) ≥ 8 g/dL.

               -  Platelets (plt) ≥ 75 x 109/L without transfusion for 7 days

               -  AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN)

               -  Serum bilirubin ≤ 1.5 x ULN (≤ 3 x ULN for subjects with documented Gilbert
                  syndrome)

               -  Estimated serum creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault
                  equation

               -  INR < 1.5 x ULN and PTT < 1.5 x ULN

        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 has a history of concurrent second cancers requiring active, ongoing systemic
             treatment

          -  Subject has prior treatment with motolimod or other agents targeting PD-1/PD-L1.

          -  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:Immune-modulation in this study will be measured in tumor tissue collected pre treatment and time of surgical resection by identifying and counting the number of tumor infiltrating CD8+ T cells.

Secondary Outcome Measures

Measure:Adverse Event(s)
Time Frame:Up to approximately 112 days
Safety Issue:
Description:An 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.
Measure:Number of Patients With adverse events that lead to delay in resection > 7 days
Time Frame:Screening through Study Day 52
Safety Issue:
Description:Number of Patients With adverse events that lead to delay in resection > 7 days.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Motolimod
  • Tislelizumab
  • Resection
  • Head and Neck Cancer
  • Checkpoint inhibitor
  • TLR 8 agonist
  • Squamous Cell Carcinoma
  • Pre-Surgical

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