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

NCT ID: NCT02279433

Last Updated: 2025-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2019-03-31

Brief Summary

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.

Detailed Description

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.

Conditions

Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

DS6051b

Intervention Type: DRUG

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

Interventions

DS6051b

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

Intervention Type: DRUG

Other Intervention Names

Investigational product; DS-6051a (a free base of 6051b)

Eligibility Criteria

Inclusion Criteria

1. Histologically or cytologically confirmed diagnosis of advanced solid tumors that have relapsed from or are refractory to standard treatment or for which no standard treatment is available

2. Part 1 Dose Escalation subjects must meet 1 of the following criteria:

• 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

Exclusion Criteria

1. Hematological malignancies

2. Known positive HIV infection, or active hepatitis B or C infection

3. Comorbidity that would interfere with therapy

4. Receipt of an allogeneic bone marrow or allogeneic stem cell transplant

5. Concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor

6. History of myocardial infarction and unstable angina within 6 months before study drug treatment; symptomatic congestive heart failure (Congestive Heart Failure New York Heart Association Class III or IV); congenital long QT syndrome; or ventricular arrhythmias defined as grade ≥2 according to NCI CTCAE, v4

7. Clinically active primary central nervous system tumors or brain metastases with the exception of subjects with glioblastoma multiform that carry ROS1 rearrangement

8. Unresolved toxicities from previous anticancer therapy

9. Systemic treatment with anticancer therapy within 3 weeks before study drug treatment

10. Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug treatment

11. Participation in a therapeutic clinical study within 3 weeks for biological treatments, and within 2 weeks or 5 half-lives, whichever is longer, for small molecule agents, before study drug treatment

12. Concomitant treatment with strong inhibitors or inducers of CYP3A4 and P-glycoprotein

13. Clinically significant malabsorption syndrome or other gastrointestinal disease that would impact drug absorption

14. QTcF values higher than 450 ms at screening

15. Breastfeeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AnHeart Therapeutics Inc.

INDUSTRY

Sponsor Role: collaborator

Nuvation Bio Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director Oncology

Role: STUDY_DIRECTOR

AnHeart Therapeutics Inc.

Locations

HonorHealth Research Institute

Scottsdale, Arizona, United States

Chao Family Comprehensive Cancer Center of

Orange, California, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Inst.

Boston, Massachusetts, United States

New York University

New York, New York, United States

South Texas Accelerated Research Therapeutics

San Antonio, Texas, United States

Countries

United States

Other Identifiers

DS6051-A-U101

Identifier Type: -

Identifier Source: org_study_id