Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Carcinoma

Carcinoma, Hepatocellular

Recurrence

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Hematinics

Cyclophosphamide

Nivolumab

Liver Extracts

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive nivolumab IV over 30 minutes on day 1, cyclophosphamide IV on day 1, and IRX-2 SC for 10 days between days 4 and 15. Cycles repeat every 28 days for up to 18 months in the absence of disease progression or unacceptable toxicity. Patients receive booster IRX-2 SC at 3, 6, 9, 12, and 15 months.

Cytokine-based Biologic Agent IRX-2

Daneng Li

This phase Ib trial studies the side effects and best dose of IRX-2 when given together with cyclophosphamide and nivolumab in treating patients with liver cancer that has come back or spread to other parts of the body and does not response to treatment. Biological therapies, such as IRX-2, may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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. Giving IRX-2, cyclophosphamide, and nivolumab may work better than the IRX?2 regimen alone in treating patients with hepatocellular carcinoma.

PRIMARY OBJECTIVES:

I. To determine the safety profile of combination IRX?2 regimen and nivolumab in anti?PD?1/PD?L1 naive patients who have failed or not tolerated at least one line of treatment.

SECONDARY OBJECTIVES:

I. To evaluate the overall response rate of IRX?2 regimen combined with nivolumab using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune modified RECIST criteria.

II. To evaluate the rate of 6?month progression?free survival in patients treated with combination IRX?2 regimen with nivolumab.

III. To evaluate median progression?free survival and overall survival.

EXPLORATORY OBJECTIVES:

I. To evaluate the circulating T cell profiles in patients before and after therapy with the combination IRX?2 regimen and nivolumab.

II. To explore identification of tumor tissue neoantigens through a multiplex proteomic assay (MHC?PepSeq) paired with tumor genomic and transcriptomic sequencing.

III. To explore putative biomarkers (including circulating tumor deoxyribonucleic acid \[DNA\] and immune cell profiles) in peripheral blood to generate hypotheses for response to treatment with combination IRX?2 regimen and nivolumab.

OUTLINE: This is a dose-escalation study of IRX-2.

Patients receive nivolumab intravenously (IV) over 30 minutes on day 1, cyclophosphamide IV on day 1, and IRX-2 subcutaneously (SC) for 10 days between days 4 and 15. Cycles repeat every 28 days for up to 18 months in the absence of disease progression or unacceptable toxicity. Patients receive booster IRX-2 SC at 3, 6, 9, 12, and 15 months.

After completion of study treatment, patients are followed up every 12 weeks.

IRX-2, Cyclophosphamide, and Nivolumab in Treating Patients With Recurrent or Metastatic and Refractory Liver Cancer

A Phase 1b Trial of the IRX-2 Regimen and Nivolumab in Patients With Advanced Hepatocellular Cancer (HCC)

Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0.

Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Best response and the percentage of participants with a best response of partial response or better will be summarized.

Per RECIST 1.1. PFS will be summarized using Kaplan?Meier methods.

PFS rate will be summarized using Kaplan?Meier methods.

National Cancer Institute (NCI)

City of Hope Medical Center

Spots Global Cancer Trial Database for refractory liver carcinoma