NCT05272384

Testing the Combination of Nivolumab and ASTX727 for Relapsed or Refractory B-Cell Lymphoma

A Phase 1 Study of Nivolumab in Combination With ASTX727 in B-cell Lymphoma (NHL or HL) With an Expansion Cohort in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) and Hodgkin Lymphoma (HL)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of nivolumab in combination with ASTX727 in treating B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. ASTX727 consists of the combination of decitabine and cedazuridine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Giving nivolumab in combination with ASTX727 may shrink and stabilize cancer.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the safety and tolerability of the combination of oral deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibition and checkpoint inhibition in relapsed or refractory B cell lymphoma (dose escalation) and diffuse large B-cell lymphoma (DLBCL) (dose expansion) or Hodgkin lymphoma (dose expansion). SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To evaluate the response rate (overall response \[ORR\], complete response \[CR\], and partial response \[PR\]), and the progression free survival (PFS) and overall survival (OS) in patients with relapsed or refractory DLBCL treated with the combination of oral DNMT inhibition and checkpoint inhibition. III. To evaluate the duration of response (DOR) and PFS in patients deriving clinical benefit (stable disease \[SD\], PR, CR) who continue therapy for an additional 12 months (24 total months). CORRELATIVE OBJECTIVES: I. To evaluate the changes in systemic immune activation, exhaustion, and T cell phenotypes in patients before and during treatment, and to compare these activation profiles between responding and progressing patients. II. To profile the tumor microenvironment pre-treatment and monitor T cell dynamics and T-cell receptor (TCR) clonality by single-cell approaches before and during treatment, and compare these profiles between responding and progressing patients. III. To determine lymphoma mutational profiles in peripheral blood circulating tumor DNA (ctDNA) and to compare changes in ctDNA levels and mutational profiling between responding and progressing patients. IV. To evaluate DNA methylation (cytosine hydroxymethylation and cytosine methylation) status in cell free (cf)DNA at global level and to compare changes in cfDNA DNA methylation levels between responding and progressing patients. OUTLINE: Patients receive decitabine and cedazuridine orally (PO) once daily (QD) on days 1-3 or 1-5 of each cycle and nivolumab intravenously (IV) over 30 minutes on day 15 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR, PR, or SD after 12 cycles receive decitabine and cedazuridine for an additional 12 months. Patients also undergo positron emission tomography (PET)/computed tomography (CT) and collection of blood samples throughout the trial. After completion of study treatment, patients are followed up every 3 months for 2 years.

Conditions

• Recurrent B-Cell Non-Hodgkin Lymphoma
• Recurrent Diffuse Large B-Cell Lymphoma
• Recurrent Hodgkin Lymphoma
• Refractory B-Cell Non-Hodgkin Lymphoma
• Refractory Diffuse Large B-Cell Lymphoma
• Refractory Hodgkin Lymphoma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
PROCEDURE	Computed Tomography	Undergo PET/CT
DRUG	Decitabine and Cedazuridine	Given PO
BIOLOGICAL	Nivolumab	Given IV
PROCEDURE	Positron Emission Tomography	Undergo PET/CT

Timeline

• Start date: 2022-11-03
• Primary completion: 2027-06-28
• Completion: 2027-06-28
• First posted: 2022-03-09
• Last updated: 2026-04-13

Locations

9 sites across 1 country: United States

Regulatory

• FDA-regulated drug study