Phase I/Ib Study of Nivolumab & Veliparib in Patients With Advanced Solid Tumors & Lymphoma

Refractory Mantle Cell Lymphoma Clinical Trial

Official title: Phase I/Ib Study of Nivolumab and Veliparib in Patients With Advanced Solid Tumors and Lymphoma With and Without Alterations in Selected DNA Repair Genes

Status Completed

Clinical Trial Summary

The purpose of this research study is to determine the highest and safest dose of the experimental drug veliparib when combined with nivolumab. We will also study how safely this combination of medication can be given in advanced cancer and lymphoma and benefits of receiving this therapy. Nivolumab is currently approved in certain cancers such as melanoma, lung cancer and kidney cancer. Veliparib is not yet approved for use in the United States, and is considered experimental. Veliparib inhibits (blocks) the activity of the enzyme PARP. This blocking activity may prevent the cancer cell from repairing itself and resume growing. Nivolumab increases T cells in your immune system, which allows your immune system to attack the cancer. We think the combination of these drugs will be more effective against your cancer.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To identify maximum tolerated dose (MTD) for the combination treatment of nivolumab and veliparib in patients with advanced refractory solid cancers and lymphoma.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of nivolumab and veliparib in patients with advanced refractory solid cancers and lymphoma with and without mutations in selected DNA repair genes.

II. To evaluate the efficacy of treatment with nivolumab and veliparib in this population by objective response rate (ORR, defined as partial response [PR] + complete response [CR]), clinical benefit rate (CBR, defined as stable disease [SD] for >= 12 weeks, PR, + CR), and progression free survival (PFS, defined as the time from treatment initiation to documented disease progression) using Response Evaluation Criteria in Solid Tumors (RECIST) criteria version (v)1.1 or Lugano criteria.

III. To evaluate efficacy of treatment with nivolumab and veliparib in this population by ORR, CBR, and immune-related PFS (irPFS) using irRECIST criteria.

IV. To evaluate overall survival (OS) in this population at 3 years from the start of treatment.

V. To evaluate the proportion of patients alive and progression free at 24 weeks in this population.

VI. To evaluate ORR to nivolumab and veliparib in patients with prior exposure to single agent PD-1/PD-L1 inhibitors.

TERTIARY OBJECTIVES:

I. To evaluate if any of the following predict response to veliparib in combination with nivolumab: tissue PD-L1 protein expression, immune cell infiltration markers.

II. To demonstrate the pharmacodynamic effects of veliparib and nivolumab on biomarkers including PD-L1, TILs, T cell subpopulations, and T cell receptor genotype.

III. To explore the pattern of clonal changes through circulating cell free DNA assay.

IV. To assess the dynamic change in both immune and genomic biomarkers in blood that may correlate with response to veliparib.

OUTLINE: This is a dose-escalation study of veliparib.

Patients receive veliparib orally (PO) twice daily (BID) on day 1 and nivolumab intravenously (IV) over 30 minutes on days 1 and 15 of courses 1-4 and IV over 60 minutes on day 1 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months and then every 6 months for 3 years. ;

Related Conditions & MeSH terms

• Advanced Solid Neoplasm
• Aggressive Non-Hodgkin Lymphoma
• Lymphoma
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell
• Neoplasms
• Recurrent Solid Neoplasm
• Refractory Mantle Cell Lymphoma
• T-Cell Non-Hodgkin Lymphoma
• Unresectable Solid Neoplasm

• NCT number: NCT03061188
• Study type: Interventional
• Source: Northwestern University
• Status: Completed
• Phase: Phase 1
• Start date: May 23, 2017
• Completion date: August 4, 2020