NCT03345485

Study of the Safety, Pharmacokinetics and Efficacy of Tinostamustine in Patients With Advanced Solid Tumors.

A Phase 1/2 Study to Investigate the Safety, Pharmacokinetics and Efficacy of EDO-S101, a First-in-Class Alkylating Histone Deacetylase Inhibition (HDACi) Fusion Molecule, in Patients With Advanced Solid Tumors. Sub-study to Characterize the Effects of Tinostamustine at a Dose of 60mg/m2 Administered During a 60 Minutes Infusion on Cardiac Repolarization, in Patients With Advanced Solid Tumors. Sub-study to Characterize the Effects of Tinostamustine at a Dose of 80mg/m2 Administered During a 80 Minutes Infusion on Cardiac Repolarization, in Patients With Advanced Solid Tumors.

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 71 (actual)
• Sponsor: Mundipharma Research Limited · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor designed to improve drug access to deoxyribonucleic acid (DNA) strands, induce DNA damage and counteract its repair in cancer cells. The main purpose of this study is to assess the safety, tolerability and efficacy of Tinostamustine in subjects with advanced solid tumours. Subjects will be given Tinostamustine via intravenous infusion on Days 1 and 15 of a 4-week cycle, the dose and infusion time will vary depending on the phase of the study.

Detailed description

The study consists of 2 phases and 2 sub-studies: This study is a multi-centre, open-label phase 1/2 study of single agent EDO-S101 in subjects with advanced solid tumours. Phase 1 part of the study is designed to determine the safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D) and the Pharmacokinetic (PK) of EDO-S101 as a single agent in patients with solid tumours who have progressed after at least one (1) line of therapy and for whom no other standard therapy with proven clinical benefit is available. Phase 2 part of the study is designed to evaluate the overall response rate (ORR) of the RP2D, plus the rate of patients with stable disease (SD) at 4 or 6 months, depending on the type of solid tumour. The RP2D was determined after phase 1 to be 80 mg/m2 of EDO-S101 administered over 1 hour on Day 1 and Day 15 of each 4-week treatment cycle. In addition, two sub-studies are designed to better characterize the effect of EDO-S101: one at a dose of 60 mg/m2 administered over 60 minutes and the second at a dose of 80 mg/m2 administered over 80 minutes on cardiac repolarization (QTc) and other ECG parameters in the subjects with solid tumours. Subjects were eligible for these studies if they had a histologically confirmed solid tumour, signed informed consent and met the inclusion/exclusion criteria. After providing informed consent, subjects were screened, and all procedures were performed as per protocol.

Conditions

• Small Cell Lung Cancer
• Soft Tissue Sarcoma
• Triple-negative Breast Cancer
• Ovarian Cancer
• Endometrial Cancer

Interventions

Type	Name	Description
DRUG	Tinostamustine 60mg/m2 over 30min	Tinostamustine as a single agent was administered at doses of 60mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle.
DRUG	Tinostamustine 80mg/m2 over 30min	Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle.
DRUG	Tinostamustine 100mg/m2 over 30min	Tinostamustine as a single agent was administered at doses of 100mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle.
DRUG	Tinostamustine 60mg/m2 over 60min	Tinostamustine as a single agent was administered at doses of 60mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle.
DRUG	Tinostamustine 80mg/m2 over 60min	Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle.
DRUG	Tinostamustine 100mg/m2 over 60min	Tinostamustine as a single agent was administered at doses of 100mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle.
DRUG	Tinostamustine 80mg/m2 over 80min	Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 80 minutes on Days (D) 1 and 15 of each 28-day cycle.

Timeline

• Start date: 2017-11-08
• Primary completion: 2022-07-27
• Completion: 2023-03-29
• First posted: 2017-11-17
• Last updated: 2024-10-21
• Results posted: 2024-10-21

Locations

13 sites across 5 countries: United States, Canada, Italy, Netherlands, Spain

Regulatory

• FDA-regulated drug study