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: NCT03906526
• Recruitment Status: Completed
• First Posted: April 8, 2019
• Last Update Posted: February 25, 2022
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

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	Intervention/treatment	Phase
Carcinoma, Squamous Cell	Drug: VTX-2337; Drug: Nivolumab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: Non-Randomized
• 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 3, 2019
• Actual Primary Completion Date: January 24, 2022
• Actual Study Completion Date: January 24, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Monotherapy Arm 1: Nivolumab; Nivolumab IV every 2 weeks	Drug: Nivolumab; IV Nivolumab; Other Name: Opdivo
Experimental: Monotherapy Arm 2: Motolimod; Motolimod IT injection weekly	Drug: VTX-2337; Motolimod; Other Name: VTX-378
Experimental: Combination Arm 3: Nivolumab and Motolimod; Nivolumab IV every 2 weeks and Motolimod IT injection weekly	Drug: VTX-2337; Motolimod; Other Name: VTX-378; Drug: Nivolumab; IV Nivolumab; Other Name: Opdivo
Experimental: Combination Arm 4: Nivolumab and Motolimod; Nivolumab IV every 2 weeks and Motolimod SC injection weekly	Drug: VTX-2337; Motolimod; Other Name: VTX-378; Drug: Nivolumab; IV Nivolumab; Other Name: Opdivo

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

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.
• 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

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294-3300

United States, Massachusetts

Boston University

Boston, Massachusetts, United States, 02215

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 63110

United States, Ohio

University of Cincinnati

Cincinnati, Ohio, United States, 45267-0501

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States, 43210

United States, Pennsylvania

University of Pittsburgh Medical Center Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15232

United States, South Dakota

Sanford Cancer Center

Sioux Falls, South Dakota, United States, 57104-8805

Sponsors and Collaborators

Celgene

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

More Information

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT03906526
• Other Study ID Numbers: VTX-2337-HN-001; U1111-1223-3488 ( Registry Identifier: WHO )
• First Posted: April 8, 2019
• Last Update Posted: February 25, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• 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; Nivolumab; Head and Neck Cancer; Squamous Cell Carcinoma; Checkpoint inhibitor; anti-PD1 inhibitor; TLR 8 agonist

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Nivolumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action