Anti-OX40 Antibody in Head and Neck Cancer Patients

Study Overview
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Brief Summary
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The purpose of this study is to test the safety of the anti-OX40 antibody, MEDI6469, given prior to surgery in patients with advanced head and neck squamous cell carcinoma.

Detailed Description
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This phase Ib clinical trial uses MEDI6469 at various dose intervals prior to definitive surgical resection of patients with stage III and IV Oral Head and Neck Squamous Cell Carcinoma (OHNSCC) with the primary objective of determining the safety and feasibility of preoperative MEDI6469 administration. In addition, tumor tissue and peripheral blood will be obtained for exploratory immunologic end points including measurements of tumor infiltrating immune cell populations based on flow cytometry and immunohistochemistry as well as circulating immunological parameters that may correlate with changes induced by MEDI6469 administration.

Official Title
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Phase Ib Study of a Monoclonal Antibody to OX40 (MEDI6469) Administered Prior to Definitive Surgical Resection Patients With Locoregionally Advanced, Oral Head and Neck Squamous Cell Carcinoma

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Anti-OX40 antibody administration
* Procedure: Surgical Resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with treatment naive, resectable, stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx who are candidates for definitive surgical resection followed by standard risk adapted adjuvant therapy. Histologic or cytologic diagnosis of a primary OHNSCC with no radiological evidence of metastatic disease is acceptable. Patients with bone or cartilage invasion and any T or N stage are acceptable. Patients with oral cavity primaries will be managed using conventional transoral or transcervical techniques; oropharynx or hypopharynx tumor will be managed with transoral robotic surgery; and larynx tumors (T3/T4 with thyroid cartilage invasion) will be managed by either total laryngectomy or larynx preservation surgery. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 Laboratory values (performed within 28 days prior to enrollment) within protocol defined range Ability to give informed consent and comply with the protocol. Patients with a history of psychiatric illness must be judged able to understand the investigational nature of the study and the risks associated with the therapy. No active gastrointestinal bleeding. Anticipated lifespan greater than 12 weeks. Exclusion Criteria: Locoregionally unresectable or Metastatic disease (stage IVB) Active infection. Active autoimmune disease including patients with Inflammatory Bowel Disease as determined by an autoimmune questionnaire. Previous treatment with mouse monoclonal antibodies Need for chronic maintenance oral steroids > 5mg prednisone daily equivalent. Any medical or psychiatric condition that in the opinion of the investigator would preclude compliance with study procedures.

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Anti-OX40 antibody administration 3 weeks prior to surgical resection | Drug: Anti-OX40 antibody administration<br>* Anti-OX40 antibody administration at 0.4 mg/kg IV x 3 doses given on Days 1, 3 or 4, and 5 or 6 of study<br>* Other names: MEDI6469;Procedure: Surgical Resection<br>* Surgical Resection of Tumor<br>|
| Experimental: Group 2<br>Anti-OX40 antibody administration 2 weeks prior to surgical resection | Drug: Anti-OX40 antibody administration<br>* Anti-OX40 antibody administration at 0.4 mg/kg IV x 3 doses given on Days 1, 3 or 4, and 5 or 6 of study<br>* Other names: MEDI6469;Procedure: Surgical Resection<br>* Surgical Resection of Tumor<br>|
| Experimental: Group 3<br>Anti-OX40 antibody administration 1 week prior to surgical resection | Drug: Anti-OX40 antibody administration<br>* Anti-OX40 antibody administration at 0.4 mg/kg IV x 3 doses given on Days 1, 3 or 4, and 5 or 6 of study<br>* Other names: MEDI6469;Procedure: Surgical Resection<br>* Surgical Resection of Tumor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and feasibility of definitive surgical resection for locoregionally advanced OHNSCC following MEDI6469 administration | Patients will be seen in clinic 7 times over 55 days to identify any possible side effects or complications thought to be related to the study drug to help identify the optimal treatment schedule. | 55 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunologic phenotypes of lymphocyte subsets | An uninvolved tumor-draining lymph node, primary tumor, and metastatic lymph nodes will be obtained during surgery, and peripheral blood will be collected 7 times over 55 days to identify the composition and immunologic phenotypes of lymphocyte subsets. This will also be compared to historical controls. | 55 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Cancer, anti-OX40 antibody, MEDI6469, Immunotherapy