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
Clinicaltrials.gov identifier recruitment status First Posted Last update posted
NCT03906526 Recruiting April 8, 2019 October 22, 2021

study description
Brief Summary

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.

Condition or Disease: Carcinoma, Squamous Cell
Intervention/treatment: Drug: VTX-2337
Drug: Nivolumab
Phase: Phase 1
Detailed Description


study design
Study Type: Interventional
Estimated Enrollment : 72 participants
Intervention Model : Parallel Assignment
Masking: None (Open Label) ()
Primary Purpose: Treatment
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)
Actual Study Start Date: July 2019
Estimated Primary Completion Date: May 2022
Estimated Study Completion Date: August 2022

Arms and interventions
Arm Intervention/treatment
Experimental: Combination Arm 3: Nivolumab and Motolimod
Nivolumab IV every 2 weeks and Motolimod IT injection weekly
Drug: VTX-2337

Drug: Nivolumab
IV Nivolumab
Experimental: Combination Arm 4: Nivolumab and Motolimod
Nivolumab IV every 2 weeks and Motolimod SC injection weekly
Drug: VTX-2337

Drug: Nivolumab
IV Nivolumab
Experimental: Monotherapy Arm 2: Motolimod
Motolimod IT injection weekly
Drug: VTX-2337
Experimental: Monotherapy Arm 1: Nivolumab
Nivolumab IV every 2 weeks
Drug: Nivolumab
IV Nivolumab
outcome measures
Primary Outcome Measures: 1. Numbers of CD8+ T cells within the tumor pre-treatment and post-surgery [ Time Frame: Screening through Study Day 52 ]
Tumor immune modulation will be evaluated by counting the number of tumor infiltration CD8+ T cells before and after treatment.
Secondary Outcome Measures: 1. Number of Patients With adverse events that lead to delay in resection [ Time Frame: Screening through Study Day 52 ]
Study will evaluate the number of patients who experience adverse events that lead to a significant delay in surgical resection.
2. Evaluation of safety and tolerability of nivolumab, motolimod and the combination of nivolumab with motolimod [ Time Frame: Up to approximately 112 days ]
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.

Eligibility Criteria
Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

United States, Alabama University of Alabama at Birmingham Birmingham
United States, California University of California Los Angeles Los Angeles
United States, Iowa University of Iowa Hospitals and Clinics Iowa City
United States, Kansas University of Kansas Westwood
United States, Massachusetts Boston University Boston
United States, Missouri Washington University Saint Louis
United States, North Carolina University of North Carolina Chapel Hill
United States, Ohio University of Cincinnati Cincinnati
United States, Ohio The Ohio State University Comprehensive Cancer Center Columbus
United States, Pennsylvania University of Pittsburgh Medical Center Hillman Cancer Center Pittsburgh
United States, South Dakota Sanford Cancer Center Sioux Falls
Sponsors and Collaborators
Study Director : Amar Patel, MD Celgene Corporation
More Information
Responsible Party : Celgene
ClinicalTrials.gov Identifier : NCT03906526     
Other Study ID Numbers : VTX-2337-HN-001, U1111-1223-3488
First Posted : April 8, 2019
Last Update Posted : October 22, 2021
Last Verified : October 2021
Individual Participant
Data (IPD) Sharing
Plan to Share IPD: Yes
Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
Supporting Materials: Study Protocol, Statistical Analysis Plan (SAP), Informed Consent Form (ICF), Clinical Study Report (CSR), Analytic Code
Time Frame: See Plan Description
Access Criteria: See Plan Description
URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celgene: Motolimod
Head and Neck Cancer
Squamous Cell Carcinoma
Checkpoint inhibitor
anti-PD1 inhibitor
TLR 8 agonist
Additional relevant MeSH terms :
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell