Oral Decitabine and Tetrahydrouridine as Epigenetic Priming for, Pembrolizumab-Mediated Immune Checkpoint Blockade in Patients With Inoperable, or Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancers and Esophageal Carcinomas

• Status: Recruiting
• Trial end date: 2026-12-31

Summary

Background:

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Lung cancer is the leading cause of cancer-related death in the United States. Most people with lung cancer are already in the advanced stages of the disease by the time they see a doctor. Researchers want to see if combining an approved drug with two new drugs can help.

Objective:

To study if tetrahydrouridine-decitabine (THU-DAC) with pembrolizumab is safe and effective in people with non-small cell lung cancer that cannot be removed by surgery.

Eligibility:

People 18 years and older who have NSCLC that cannot be removed by surgery

Design:

Participants will be screened with

• Medical history

• Physical exam

• Blood and urine tests

• Tests of heart and lung function

They may have a small tumor sample taken (biopsy). They may have tumor scans.

Before starting treatment, participants will repeat the screening tests. They will also give a stool sample.

The study will be done in 3-week cycles for up to 6 cycles.

• Participants will take the 2 study drugs by mouth 3-5 days a week.

• Participants will get pembrolizumab in a vein for 30 minutes 1 day each cycle.

Participants will keep a study medication diary.

During cycle 1, participants will have blood taken multiple times on days 1 and 2.

Every 3 cycles, participants will repeat screening tests.

Participants will have a mandatory tumor biopsy.

When they finish treatment, participants will have a physical exam and blood tests.

• Phase: Phase 1/Phase 2

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Azacitidine; Decitabine; Pembrolizumab; Tetrahydrouridine