NCT03925428

Testing a New Anti-cancer Drug Combination, Entinostat and GSK525762C, for Advanced and Refractory Solid Tumors and Lymphomas

Phase I Study of GSK525762C and Entinostat in Advanced and Refractory Solid Tumors and Lymphomas

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of GSK525762C (molibresib besylate) and entinostat in treating patients with solid tumors or lymphomas that have spread to other parts of the body (advanced) or are not responding to treatment (refractory). GSK525762C and entinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. This study may help doctors find out if giving the combination of GSK525762C and entinostat is better or worse than the usual approach for treating solid tumors or lymphomas.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of GSK525762C and entinostat in combination in patients with advanced and refractory solid tumors and lymphomas based on dose limiting toxicities (DLTs) of the combination of GSK525762C and entinostat. SECONDARY OBJECTIVES: I. To describe the safety profile of GSK525762C and entinostat in advanced and refractory solid tumors and lymphomas. II. To determine the overall response rate (ORR) of GSK525762C and entinostat in advanced and refractory solid tumors and lymphomas. III. To determine the progression-free survival (PFS), duration of response (DOR), and overall survival (OS) of GSK525762C and entinostat in this patient population. EXPLORATORY OBJECTIVES: I. To assess the effect of GSK525762C and entinostat therapy on apoptosis, as measured by an apoptosis multiplex immunoassay. II. To assess the effect of GSK525762C and entinostat therapy on c-MYC and YAP1 as measured by ribonucleic acid (RNA) and protein expression. III. To assess the effect of GSK525762C and entinostat therapy on tumor burden and gene expression patterns as measured by whole exome sequencing (WES) and RNA sequencing (RNASeq) on circulating tumor deoxyribonucleic acid (DNA) (ctDNA) specimens. OUTLINE: This is a dose-escalation study. Patients receive entinostat orally (PO) on days 1, 8, 15, and 22, and molibresib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks.

Conditions

• Advanced Lymphoma
• Advanced Malignant Solid Neoplasm
• Ann Arbor Stage III B-Cell Non-Hodgkin Lymphoma
• Ann Arbor Stage III T-Cell Non-Hodgkin Lymphoma
• Ann Arbor Stage IV B-Cell Non-Hodgkin Lymphoma
• Ann Arbor Stage IV T-Cell Non-Hodgkin Lymphoma
• Refractory B-Cell Non-Hodgkin Lymphoma
• Refractory Lymphoma
• Refractory Malignant Solid Neoplasm
• Refractory Pancreatic Carcinoma
• Refractory T-Cell Non-Hodgkin Lymphoma
• Stage II Pancreatic Cancer AJCC v8
• Stage IIA Pancreatic Cancer AJCC v8
• Stage IIB Pancreatic Cancer AJCC v8
• Stage III Pancreatic Cancer AJCC v8
• Stage IV Pancreatic Cancer AJCC v8
• Unresectable Pancreatic Carcinoma

Interventions

Type	Name	Description
DRUG	Entinostat	Given PO
DRUG	Molibresib	Given PO

Timeline

• Start date: 2020-09-18
• Primary completion: 2020-09-18
• Completion: 2020-09-18
• First posted: 2019-04-24
• Last updated: 2020-09-28

Regulatory

• FDA-regulated drug study