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

Sponsor

Celgene (Industry)

Overall Status

Completed

CT.gov ID

NCT03906526

Collaborator

(none)

Enrollment

Locations

Arms

30.8

Actual Duration (Months)

2.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

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 :

Jul 3, 2019

Actual Primary Completion Date :

Jan 24, 2022

Actual Study Completion Date :

Jan 24, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Numbers of CD8+ T cells within the tumor pre-treatment and post-surgery [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

Number of Patients With adverse events that lead to delay in resection [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.
Evaluation of safety and tolerability of nivolumab, motolimod and the combination of nivolumab with motolimod [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294-3300
2	Boston University	Boston	Massachusetts	United States	02215
3	Washington University	Saint Louis	Missouri	United States	63110
4	University of Cincinnati	Cincinnati	Ohio	United States	45267-0501
5	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
6	University of Pittsburgh Medical Center Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
7	Sanford Cancer Center	Sioux Falls	South Dakota	United States	57104-8805