Anti-OX40 Antibody in Head and Neck Cancer Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Procedure: Surgical Resection; Drug: Anti-OX40 antibody administration

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97213
      • Portland Providence Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Anti-OX40 antibody administration 3 weeks prior to surgical resection	Procedure: Surgical Resection; Surgical Resection of Tumor; Drug: Anti-OX40 antibody administration; 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; Other Names: MEDI6469
Experimental: Group 2; Anti-OX40 antibody administration 2 weeks prior to surgical resection	Procedure: Surgical Resection; Surgical Resection of Tumor; Drug: Anti-OX40 antibody administration; 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; Other Names: MEDI6469
Experimental: Group 3; Anti-OX40 antibody administration 1 week prior to surgical resection	Procedure: Surgical Resection; Surgical Resection of Tumor; Drug: Anti-OX40 antibody administration; 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; Other Names: MEDI6469

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Outcome of Imaging	Clinical surveillance for recurrence as per PET +/- CT within 6 months of completion of treatment exam. Clinical outcomes will be compared to historical controls.	5 years

Collaborators and Investigators

• Sponsor: Providence Health & Services
• Collaborators: MedImmune LLC
• Investigators: Principal Investigator: Richard B. Bell, MD, Providence Cancer Center

Publications and helpful links

General Publications

• Duhen R, Ballesteros-Merino C, Frye AK, Tran E, Rajamanickam V, Chang SC, Koguchi Y, Bifulco CB, Bernard B, Leidner RS, Curti BD, Fox BA, Urba WJ, Bell RB, Weinberg AD. Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells. Nat Commun. 2021 Feb 16;12(1):1047. doi: 10.1038/s41467-021-21383-1.

Helpful Links

• Providence Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2014
• Primary Completion (Actual): September 17, 2017
• Study Completion (Actual): December 21, 2023

Study Registration Dates

• First Submitted: October 14, 2014
• First Submitted That Met QC Criteria: October 22, 2014
• First Posted (Estimated): October 24, 2014

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Head and Neck Cancer; Immunotherapy; anti-OX40 antibody; MEDI6469
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: 14-042A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO