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: Terminated
• First Posted: April 8, 2019
• Last Update Posted: February 24, 2023
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Tracking Information

• First Submitted Date: December 5, 2018
• First Posted Date: April 8, 2019
• Last Update Posted Date: February 24, 2023
• Actual Study Start Date: July 3, 2019
• Actual Primary Completion Date: January 24, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 27, 2019)

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.

Original Primary Outcome Measures (submitted: April 4, 2019)

Numbers of CD8+ T cells within the tumor pre-treatment and post-surgery [ Time Frame: Screening through Study Day 52 ]

Immune-modulation in this study will be measured in tumor tissue collected pre treatment and time of surgical resection by identifying and counting the number of tumor infiltrating CD8+ T cells.

Current Secondary Outcome Measures (submitted: September 27, 2019)

• 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.
• 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.

Original Secondary Outcome Measures (submitted: April 4, 2019)

• Adverse Event(s) [ Time Frame: Up to approximately 112 days ]
  An 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.
• Number of Patients With adverse events that lead to delay in resection > 7 days [ Time Frame: Screening through Study Day 52 ]
  Number of Patients With adverse events that lead to delay in resection > 7 days.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Squamous Cell

Intervention

• Drug: VTX-2337
  Motolimod
  Other Name: VTX-378
• Drug: Nivolumab
  IV Nivolumab
  Other Name: Opdivo

Study Arms

• Experimental: Monotherapy Arm 1: Nivolumab
  Nivolumab IV every 2 weeks
  Intervention: Drug: Nivolumab
• Experimental: Monotherapy Arm 2: Motolimod
  Motolimod IT injection weekly
  Intervention: Drug: VTX-2337
• Experimental: Combination Arm 3: Nivolumab and Motolimod
  Nivolumab IV every 2 weeks and Motolimod IT injection weekly
  Interventions:

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

  • Drug: VTX-2337
  • Drug: Nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 23, 2022): 15
• Original Estimated Enrollment (submitted: April 4, 2019): 72
• Actual Study Completion Date: January 24, 2022
• Actual Primary Completion Date: January 24, 2022 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03906526
• Other Study ID Numbers: VTX-2337-HN-001; U1111-1223-3488 ( Registry Identifier: WHO )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: 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/

• Current Responsible Party: Celgene
• Original Responsible Party: Same as current
• Current Study Sponsor: Celgene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Celgene
• Verification Date: February 2023