ASTX727 and Nivolumab in Squamous Cell Carcinoma of the Head and Neck

NCT06357858 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: CASE6323
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to see if the combination of experimental drug ASTX727 and Nivolumab enhances the antitumor immune response in participants will recurrent or metastatic squamous cell carcinoma of the head and neck. Participants will take a pill called ASTX727 for 4 or 5 days every month followed by an injection of Nivolumab one week after the first dose of study medication.

Conditions

Recurrent Squamous Cell Carcinoma of the Head and Neck; Metastatic Squamous Cell Carcinoma; Head and Neck Squamous Cell Carcinoma

Keywords

ASTX727; Nivolumab

Outcome Measures

Primary Outcomes (4)

• Pharmacodynamics Effect of ASTX727 on global DNA methylation status

  To find a biologically effective dose of ASTX727 in this clinical trial, levels of global DNA methylation at pre- versus post-ASTX727 will be compared using Wilcoxon signed-rank test.

  12 months after completion of treatment

• Immunogenicity of ASTX27 in combination with Nivolumab

  To investigate the whether DNA methylation status affect immunologic biomarkers, changes in methylation status at pre-, post-ASTX727 and on treatment of ASTX727 plus Nivolumab will be correlated with the changes in immunologic biomarkers.

  12 months after completion of treatment

• Maximum Tolerated Dose

  Establish the maximum tolerated dose (MTD) in Phase I part 1.

  12 months after completion of treatment

• Safety of ASTX

  Assess safety of ASTX in combination with Nivolumab.

  12 months after completion of treatment

Secondary Outcomes (2)

• Objective Response Rate (ORR)

  12 months after completion of treatment

• Overall Survival (OS)

  12 months after completion of treatment

Study Arms (1)

Oral Decitabine + Nivolumab

EXPERIMENTAL

Oral decitabine (ASTX727) will be administered during D1-5 (DL1) or D1-4 (DL1-1) followed by Nivolumab on D8 with every 4 week cycle. The expected minimum treatment cycle is 2 and maximum treatment cycle of 6. However, treatment can be continued until disease progression.

Drug: INQOVI (decitabine and cedazuridine); Drug: Nivolumab

Interventions

INQOVI (decitabine and cedazuridine) DRUG

Oral decitabine (ASTX727) will be administered during D1-5 (DL1) or D1-4 (DL1-1).

Also known as: ASTX727

Oral Decitabine + Nivolumab

Nivolumab DRUG

Nivolumab will be administered on D8 with every 4 week cycle.

Also known as: OPDIVO

Oral Decitabine + Nivolumab

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed recurrent or metastatic HNSCC considered incurable by local therapies and eligible to receive anti-PD-L1 as first-line treatment (PD-L1 positive with combined positive score (CPS) ≥1 as evaluated in pre-screening).
• Participants must have primary tumor locations in following; oral cavity, hypopharynx, or larynx (nasopharynx is not allowed).
• Participants must have not received prior therapies for this disease, no systemic therapy administered in the recurrent or metastatic setting (except for systemic therapy completed within 6 months or \> 6 months if given as part of multimodal treatment for locally advanced disease).
• Participants must have not received prior treatment with immune checkpoint inhibitors.
• Participants can provide archival tumor tissue not older than 12 months from a core or excisional biopsy for PD-L1 pre-screening using the PD-L1 IHC 22C3 pharmDx assay.
• Participants must have lesions amenable to obtain pre-treatment tumor biopsies in screening period after eligibility confirmation and before start of treatment and on- treatment tumor biopsies on C1D8 \& C3D8 after start of treatment if lesions are still present at that time. If a recent archival biopsy is obtained within 3 months prior to start of treatment, this biopsy can be used as a pre-treatment biopsy.
• Participants should be age \>18 years.
• Participants should have ECOG Performance status ≤ 2.
• Participants should have ability to swallow pills (participants will have to demonstrate the ability to swallow a placebo during screening).
• Participants must have normal organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dl
• Leukocytes ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Total bilirubin within normal institutional limits (Gilbert's syndrome related elevated bilirubin is accepted as long as levels have been stable within last 3 months).

You may not qualify if:

• Participants with progressive disease within six months of completion of curatively Intended systemic treatment for locoregionally advanced HNSCC.
• Participants with history of severe immune related adverse effects from prior immunotherapy, except hypothyroidism clinically stable on hormone replacement treatment and controlled type 1 diabetes. All other endocrinopathies are excluded even if controlled with medications.
• Participants with Grade ≥ 3 infections within 4 weeks before the first study drug administration. Clinically active infections \> Grade 1 within 2 weeks before the first study drug administration.
• Participants with previous or active myocarditis/myositis in history (independent of cause).
• Participants with pneumonitis, idiopathic pulmonary fibrosis, organizing, interstitial lung disease active or history of autoimmune disease. . Autoimmune thyroid disease as well as other non-life threatening autoimmune diseases such as vitiligo or autoimmune alopecia that don't require systemic immunosuppression are not excluded.
• Participants with known human immunodeficiency virus (HIV) infection, uncontrolled active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Participants with treatment with systemic immunosuppressant medications within 2 weeks before the first study drug administration. However, low-dose steroid use (prednisone equivalent \<=10mg daily) for other reasons is allowed.
• Participants receiving any other investigational agents.
• Participants with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Participants with confirmed COVID-19 within 7 days prior to start treatment will be excluded, however upon recovery with confirmation of negative COVID test, participant can be reconsidered for the study.
• Participants with a history of hypersensitivity to active or inactive excipients of ASTX727 or nivolumab or drugs with a similar chemical structure or class to either agent.
• Participants with any other condition which in the Investigator's opinion would not make the participant a good candidate for the clinical trial.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell

Interventions

decitabine and cedazuridine drug combination; Decitabine; cedazuridine; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Kyunghee Burkitt, DO, PhD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2024
• First Posted: April 10, 2024
• Study Start: June 1, 2024
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2026
• Last Updated: July 3, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Compiled and analyzed patient data will be published upon study completion. Publisher may request Protocol and Statistical Analysis Plan.

Locations

US (1)