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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Carcinoma, Squamous Cell

Intervention / Treatment
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* Drug: VTX-2337
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy Arm 1: Nivolumab<br>Nivolumab IV every 2 weeks | Drug: Nivolumab<br>* IV Nivolumab<br>* Other names: Opdivo;|
| Experimental: Monotherapy Arm 2: Motolimod<br>Motolimod IT injection weekly | Drug: VTX-2337<br>* Motolimod<br>* Other names: VTX-378;|
| Experimental: Combination Arm 3: Nivolumab and Motolimod<br>Nivolumab IV every 2 weeks and Motolimod IT injection weekly | Drug: VTX-2337<br>* Motolimod<br>* Other names: VTX-378;Drug: Nivolumab<br>* IV Nivolumab<br>* Other names: Opdivo;|
| Experimental: Combination Arm 4: Nivolumab and Motolimod<br>Nivolumab IV every 2 weeks and Motolimod SC injection weekly | Drug: VTX-2337<br>* Motolimod<br>* Other names: VTX-378;Drug: Nivolumab<br>* IV Nivolumab<br>* Other names: Opdivo;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With adverse events that lead to delay in resection | Study will evaluate the number of patients who experience adverse events that lead to a significant delay in surgical resection. | Screening through Study Day 52 | 
| Evaluation of safety and tolerability of nivolumab, motolimod and the combination of nivolumab with motolimod | 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. | Up to approximately 112 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Motolimod, Nivolumab, Head and Neck Cancer, Squamous Cell Carcinoma, Checkpoint inhibitor, anti-PD1 inhibitor, TLR 8 agonist