A First-in-human Study To Evaluate The Safety, Tolerability And Pharmacokinetics Of DS-6051b

Study Overview

A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b

DS-6051b is an orally administered inhibitor of the tyrosine kinases (ROS1) and neurotropic tyrosine kinase receptors (NTRK). This phase 1 first-in-human study evaluates safety and tolerability of DS-6051b in cancer subjects and identify a recommended phase 2 dose (RP2D). In addition, this study will also assess the pharmacokinetic (PK)/pharmacodynamic (PD) profiles and preliminary efficacy of DS-6051b.

The Dose Escalation part (Part 1) of this study will evaluate safety and tolerability, and determine the tentative RP2D. Plasma exposure of DS-6051a and the exposure - QT interval prolongation relationship will also be assessed. Approximately 30 subjects with advanced solid tumors harboring ROS1 or NTRK1, NTRK2, or NTRK3 rearrangement, neuroendocrine carcinoma, or with advanced solid tumors and tumor-induced pain will be enrolled. The Food Effect (FE) part of this study is to determine the effect of food on the PK of DS-6051a following administration of a single oral dose of DS-6051b. The safety and tolerability of DS-6051b administered with or without food will also be assessed. After the safety profile of DS-6051b is adequately evaluated, the Dose Expansion part (Part 2) will be initiated to further assess the safety and tolerability, and preliminarily evaluate the efficacy of DS-6051b at the tentative RP2D. Approximately 40 cancer subjects carrying a ROS1 or NTRK1, NTRK2, or NTRK3 rearrangement will be enrolled.

Solid Tumors

DRUG: DS6051b

DS6051-A-U101

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2014-10-15	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-09-18
First Submitted that Met QC Criteria 2014-10-28	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-09-22
First Posted (ACTUAL) 2014-10-31	Results First Posted N/A	Last Verified 2020-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: DS-6051b DS-6051b is orally administered as 50 mg and 200 mg capsules once daily on Days 1 to 21 of a 21-day cycle. Dose escalation in Part 1 will continue until tentative Recommended Part 2 Dose (RP2D) is determined. In Part 2 participants will receive the RP2D.	DRUG: DS6051b DS-6051b 50 mg and 200 mg capsules for oral administration

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: DS-6051b

DS-6051b is orally administered as 50 mg and 200 mg capsules once daily on Days 1 to 21 of a 21-day cycle. Dose escalation in Part 1 will continue until tentative Recommended Part 2 Dose (RP2D) is determined. In Part 2 participants will receive the RP2D.

DRUG: DS6051b

DS-6051b 50 mg and 200 mg capsules for oral administration

Primary Outcome Measures	Measure Description	Time Frame
Part 1: Number of participants with dose-limiting toxicities		within 21 days following the first dose of treatment
Tumor response	Tumor response will be assessed using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.	up to 2 years

Secondary Outcome Measures	Measure Description	Time Frame
Maximum concentration (Cmax) for DS-6051a		At Days 1 and 15 of Cycle 1 (21 days)
Time to maximum concentration (Tmax) for DS-6051a		At Days 1 and 15 of Cycle 1 (21 days)
Area under the concentration-time curve from time zero to t (AUC0-t) for DS-6051a		At Days 1 and 15 of Cycle 1 (21 days)
Change from baseline in QTc interval	ECGs performed to assess QTc interval (ms) at baseline and on study treatment and at the end of treatment visit.	within 2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Solid tumors with documented ROS1, NTRK1, NTRK2, or NTRK3 rearrangement
Neuroendocrine tumors
Solid tumors with tumor-induced pain 3. Part 2 Dose Expansion subjects must meet 1 of the following criteria:

NSCLC with documented ROS1, NTRK1, NTRK2, or NTRK3 rearrangement
k-RAS wild-type CRC with documented NTRK1, NTRK2, or NTRK3 rearrangement
Other solid tumors with documented ROS1, NTRK1, NTRK2, or NTRK3 rearrangement
Pulmonary LCNEC; 4. Male or female ≥18 years of age 5. Eastern Cooperative Oncology Group performance status 0 to 1 6. Adequate organ function 7. Adequate blood clotting function 8. Women of childbearing potential must have a negative pregnancy test 9. Willingness to provide archival tumor samples 10. Other inclusion criteria may apply

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Study Director Oncology, AnHeart Therapeutics Inc.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

Patients

Caregivers

Clinical Trial Record