Case Comprehensive Cancer Center
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.
Recurrent Squamous Cell Carcinoma of the Head and Neck
Metastatic Squamous Cell Carcinoma
Head and Neck Squamous Cell Carcinoma
INQOVI (decitabine and cedazuridine)
Nivolumab
Phase 1
Anti PD1 inhibitor (Pembrolizumab, Nivolumab) is approved for recurrent/metastatic HNCC. However, response rates to Pembrolizumab or Nivolumab monotherapy are as low as 16-19%, underscoring the presence of immune evasion mechanisms. One of the main immune escape mechanisms described in HNSCC is poor tumor microenvironment characterized by defective HLA class I processing and antigen presentation, which allows tumor cells to evade their detection and destruction by cytotoxic CD8+ T-cells. Mutations or downregulation of the expression of HLA class I component including beta-2- microglobulin (β2M) and antigen processing machinery (APM) genes have been correlated with poor prognosis of HNSCC. Recent studies showed that de novo DNA methylation programs renders terminal T cell exhaustion and subsequent exhausted T cells are refractory to PD-1 blockade mediated rejuvenation. Pretreatment with DNA methyltransferases (DNMT) inhibitor prior to PD-L1 blockade showed enhancement of T cell responses and tumor control during PD-1 inhibitors in mice. A pilot study of novel combination of antiPD-1 and decitabine was conducted in patients with refractory or recurrent AML. The showed a best response of stable disease or better in 6 of 10 patients in patients with R-AML. A phase II clinical trial of anti-PD-1 camrelizumab plus decitabine, in relapsed/refractory Hodgkin lymphoma showed CR rate of 79% with decitabine plus camrelizumab compared to 32% with camrelizumab alone. Based on the promising results of decitabine enhances immune response and antitumor activity shown in both preclinical and preliminary clinical data from the phase II trial of hematological malignancies, I hypothesize that ASTX727 (oral decitabine and cedazuridine) changes DNA methylation status which may enhance the antitumor immune response by modulating tumor immune microenvironment and promoting increased tumor-infiltrating lymphocytes, which may enhance response to anti-PD1 inhibitor in R/M HNSCC patients
Study Type : | Interventional |
Estimated Enrollment : | 15 participants |
Masking : | None (Open Label) |
Primary Purpose : | Treatment |
Official Title : | Biomarker Driven Phase 1/1b Trial of ASTX727 and Nivolumab in Patients With Recurrent / Metastatic Squamous Cell Carcinoma of the Head and Neck |
Actual Study Start Date : | June 1, 2024 |
Estimated Primary Completion Date : | February 28, 2025 |
Estimated Study Completion Date : | February 28, 2026 |
Arm | Intervention/treatment |
---|---|
Experimental: Oral Decitabine + Nivolumab 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 |
Ages Eligible for Study: | 19 Years |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.
Not yet recruiting
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106