Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Decitabine

Nivolumab

Decitabine and cedazuridine drug combination

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Antimetabolites

Enzyme Inhibitors

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.

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

INQOVI (decitabine and cedazuridine)

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

Kyunghee Burkitt, DO, PhD

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.

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

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

Biomarker Driven Phase 1/1b Trial of ASTX727 and Nivolumab in Patients With Recurrent / Metastatic Squamous Cell Carcinoma of the Head and Neck

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.

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.

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

Assess safety of ASTX in combination with Nivolumab.

The true objective response rate will be estimated based on the number of responses using a binomial distribution and its confidence interval will be estimated using Wilson's method.

Overall survival will be measured from the date of enrollment to the date of death.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
ASTX727 and Nivolumab in Squamous Cell Carcinoma of the Head and Neck	NCT06357858	Recurrent Squam... Metastatic Squa... Head and Neck S...	INQOVI (decitab... Nivolumab	19 Years -	Case Comprehensive Cancer Center
ASTX727 and Nivolumab in Squamous Cell Carcinoma of the Head and Neck	NCT06357858	Recurrent Squam... Metastatic Squa... Head and Neck S...	INQOVI (decitab... Nivolumab	19 Years -	Case Comprehensive Cancer Center

Spots Global Cancer Trial Database for inqovi (decitabine and cedazuridine)