Ignite Creation Date:
2024-05-06 @ 8:22 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06357858
Status:
WITHDRAWN
Last Update Posted:
2024-07-03
First Post:
2024-04-05
Brief Title:
ASTX727 and Nivolumab in Squamous Cell Carcinoma of the Head and Neck
Sponsor:
Case Comprehensive Cancer Center
Organization:
Case Comprehensive Cancer Center
Study Overview
Official Title:
Biomarker Driven Phase 11b Trial of ASTX727 and Nivolumab in Patients With Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck
Status:
WITHDRAWN
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Funding unavailable
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
Anti PD1 inhibitor Pembrolizumab Nivolumab is approved for recurrentmetastatic 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 relapsedrefractory 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 RM HNSCC patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None