NCT07216833

Decitabine and Nivolumab in Participants With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

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

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Kyunghee Burkitt, DO, PhD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This research study is for people who have recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that has been confirmed by tissue or cell analysis and is considered incurable with local treatments. People who are eligible to receive anti-PD-L1 therapy as a first line treatment and whose primary tumor is located in the oral cavity, oropharynx, hypopharynx, or larynx, may be eligible to participate. The purpose of this study is to evaluate the immunogenicity of decitabine in combination with nivolumab, and to evaluate the safety and tolerability of decitabine in combination with nivolumab and to determine the maximum tolerated dose. Decitabine is a drug that is currently approved by the Food and Drug Administration (FDA) for the treatment of myelodysplastic syndrome (MDS). Decitabine is considered an investigational (experimental) drug in this study because it is not approved by the FDA for the treatment of HNSCC. Decitabine is a chemotherapy drug that works by targeting DNA methylation, a process that can restore normal function to genes that are involved in cell growth and differentiation. This can help reduce the growth of cancer cells. Nivolumab is a drug that is approved by the FDA for the treatment of HNSCC, as well as other types of cancer. Nivolumab is an immunotherapy drug that works by helping the body's immune system recognize and attack cancer cells.

Detailed description

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide with approximately 60,000 people diagnosed each year in the United States. People with human papilloma virus (HPV)-positive HNSCC usually have a good prognosis, but HPV-negative people have about a 50% chance that their cancer will come back even after being treated. People who have recurrent or metastatic (R/M) HNSCC who are treated for their cancer tend to have an even worse prognosis, with a median overall survival of about 10 months. An anti-programmed-death-1 (anti-PD1) inhibitor called pembrolizumab was recently approved to treat people with R/M HNSCC. Another type of anti-PD1 inhibitor is a drug called nivolumab, which is also approved to treat people with R/M HNSCC. However, response rates to both pembrolizumab and nivolumab monotherapy are as low as 19% and 13.3% respectively. This shows that there are immune-evasive mechanisms present, meaning that tumor cells can more easily evade being detected and destroyed. Decitabine is a drug that may help anti-PD1 inhibitors like nivolumab better detect and destroy tumor cells. Previous research has shown that using a DNA methyltransferase inhibitor before giving a PD1 inhibitor to treat cancer can help the body's immune system more effectively kill cancer cells. Decitabine is a drug that is a type of DNA methyltransferase inhibitor. The purpose of this study is to evaluate the safety and tolerability of using decitabine in combination with nivolumab to treat HNSCC.

Conditions

• Head and Neck Cancer
• Head and Neck Neoplasms
• Head and Neck Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Decitabine	Participants will receive dose level 1 (DL1). If 2 of 3 participants experience dose limiting toxicity (DLT) on DL1, then the dose will be de-escalated to DL1-1. If 2 of 3 participants experience DLT on DL1-1, then no further de-escalation will occur and no additional participants will be enrolled. DL1: Intravenous (IV) administration of decitabine 20 mg/m2 from Days 1-5 DL1-1: Intravenous (IV) administration of decitabine 20 mg/m2 from Days 1-4
DRUG	Nivolumab	Nivolumab will be used as a fixed dose in combination with de-escalating dose levels (DL1, DL1-1) of decitabine. Participants will receive 480 mg of nivolumab on Day 8 every 4-week cycle.

Timeline

• Start date: 2026-01-01
• Primary completion: 2027-07-31
• Completion: 2027-12-31
• First posted: 2025-10-15
• Last updated: 2025-10-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study