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

NCT02279433 | Completed Phase 1 FDA Drug

• 1 other identifier: DS6051-A-U101
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 6

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.

Conditions

Solid Tumors

Keywords

Neoplasms; Lung Neoplasms; Colorectal Neoplasms; Neuroendocrine Tumors; Pancreatic Neoplasms

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

  within 2 years

Study Arms (1)

DS-6051b

EXPERIMENTAL

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

Interventions

DS6051b DRUG

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

Also known as: Investigational product, DS-6051a (a free base of 6051b)

DS-6051b

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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;
• Male or female ≥18 years of age
• Eastern Cooperative Oncology Group performance status 0 to 1
• Adequate organ function
• Adequate blood clotting function
• Women of childbearing potential must have a negative pregnancy test

You may not qualify if:

• Hematological malignancies
• Known positive HIV infection, or active hepatitis B or C infection
• Comorbidity that would interfere with therapy
• Receipt of an allogeneic bone marrow or allogeneic stem cell transplant
• Concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor
• 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
• Clinically active primary central nervous system tumors or brain metastases with the exception of subjects with glioblastoma multiform that carry ROS1 rearrangement
• Unresolved toxicities from previous anticancer therapy
• Systemic treatment with anticancer therapy within 3 weeks before study drug treatment
• Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug treatment
• 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
• Concomitant treatment with strong inhibitors or inducers of CYP3A4 and P-glycoprotein
• Clinically significant malabsorption syndrome or other gastrointestinal disease that would impact drug absorption
• QTcF values higher than 450 ms at screening
• Breastfeeding

Sponsors & Collaborators

• Nuvation Bio Inc.: lead
• AnHeart Therapeutics Inc.: collaborator

Study Sites (6)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

Chao Family Comprehensive Cancer Center of

Orange, California, 92868, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Inst.

Boston, Massachusetts, 02215, United States

Location

New York University

New York, New York, 10016, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Neoplasms; Lung Neoplasms; Colorectal Neoplasms; Neuroendocrine Tumors; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Study Director Oncology

  AnHeart Therapeutics Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2014
• First Posted: October 31, 2014
• Study Start: September 1, 2014
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)