Clinical Trials /

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

NCT02279433

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

Title

  • Brief Title: A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b
  • Official Title: A Phase 1, Two-Part, Multi-Center, Non Randomized, Open-Label, Multiple Dose First-In-Human Study Of DS-6051b, An Oral ROS1 And NTRK Inhibitor, In Subjects With Advanced Solid Tumors
  • Clinical Trial IDs

    NCT ID: NCT02279433

    ORG ID: DS6051-A-U101

    Trial Conditions

    Solid Tumors

    Trial Interventions

    Drug Synonyms Arms
    DS6051b DS-6051b

    Trial Purpose

    DS-6051b is an orally administered inhibitor of the tyrosine kinases ROS1 and NTRKs. 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.

    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.

    Trial Arms

    Name Type Description Interventions
    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 RP2D determined. DS6051b

    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

    10. Other inclusion criteria may apply

    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

    16. Other exclusion criteria may apply

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Part 1: Number of participants with dose-limiting toxicities

    Part 2: tumor response

    Secondary Outcome Measures

    Composite of plasma exposure parameters of DS-6051a

    Changes in QTc interval

    Trial Keywords

    Neoplasms

    Lung Neoplasms

    Colorectal Neoplasms

    Neuroendocrine Tumors

    Pancreatic Neoplasms