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Phase 1/2 Study of LOXO-195 in Patients With Previously Treated NTRK Fusion Cancers

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ClinicalTrials.gov Identifier: NCT03215511
Recruitment Status : Recruiting
First Posted : July 12, 2017
Last Update Posted : March 1, 2018
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Loxo Oncology, Inc.

Brief Summary:
This is a Phase 1/2, multi-center, open-label study designed to evaluate the safety and efficacy of LOXO-195 when administered orally to patients age ≥ 1 month and older with NTRK fusion cancers treated with a prior TRK inhibitor.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Thyroid Neoplasms Sarcoma Colorectal Neoplasms Salivary Gland Neoplasms Biliary Tract Neoplasms Brain Neoplasm, Primary Melanoma Glioblastoma Bile Duct Neoplasms Astrocytoma Head and Neck Squamous Cell Carcinoma Pontine Glioma Pancreatic Neoplasms Ovarian Neoplasms Carcinoma, Renal Cell Cholangiocarcinoma Skin Carcinoma Carcinoma, Bronchogenic Bronchial Neoplasms Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms, Nerve Tissue Nevi and Melanomas Intestinal Neoplasms Thyroid Cancer GIST Malignant Peripheral Nerve Sheath Tumors Breast Secretory Carcinoma Uterine Neoplasms Fibrosarcoma Infantile Fibrosarcoma Congenital Mesoblastic Nephroma Central Nervous System Neoplasms Drug: LOXO-195 Phase 1 Phase 2

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Detailed Description:
The trial will be conducted in 2 parts: dose escalation (Phase I ) and dose expansion (Phase 2) . Patients with unresectable or metastatic solid tumors are eligible if progressed or intolerant to prior TRK inhibitor. During Phase 1, a maximum tolerated dose (MTD)/recommended dose for further study will be identified for in patients age 12 and older and patients age <12. During Phase 2, the same patient population as designated for Phase 1 will be treated with the dose of LOXO-195 which has been identified during phase 1 to assess specified endpoints.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 93 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of the TRK Inhibitor LOXO-195 in Adult and Pediatric Subjects With Previously Treated NTRK Fusion Cancers
Actual Study Start Date : July 10, 2017
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: LOXO-195
Phase 1- Dose Escalation and determination of MTD; Multiple dose levels of LOXO-195 to be evaluated Phase 2 - Treatment with LOXO-195 at the recommended dose from Phase 1 identified for further study
Drug: LOXO-195
Capsules / liquid suspension LOXO-195



Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: The first 28 days of treatment (Cycle 1) ]
    For Phase 1

  2. Recommended dose for further study in patients age 12 and older and age <12 [ Time Frame: The first 28 days of treatment (Cycle 1) and every cycle (28 days) for approximately 12 months (or earlier if the patient discontinues from the study) ]
    For Phase 1

  3. Best overall response of confirmed PR or CR by independent radiology review in patients age 12 and older and age <12 in NTRK fusion cancer patients previously treated with TRK inhibitor who have progressed [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks while on treatment, and every 12 weeks after the last dose (for up to 2 years) in patients who have not progressed ]
    For Phase 2


Secondary Outcome Measures :
  1. Incidence of AEs [ Time Frame: From the time of informed consent, for approximately 24 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose) ]
    For Phase 1 and Phase 2

  2. Severity of AEs [ Time Frame: From the time of informed consent, for approximately 24 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose) ]
    For Phase 1 and Phase 2

  3. Duration of AEs [ Time Frame: From the time of informed consent, for approximately 24 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose) ]
    For Phase 1 and Phase 2

  4. Changes in clinical laboratory results compared to baseline [ Time Frame: For approximately 24 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose) ]
    For Phase 1 and Phase 2

  5. Changes in vital signs compared to baseline [ Time Frame: For approximately 24 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose) ]
    For Phase 1 and Phase 2

  6. Best overall response of confirmed PR or CR by independent radiology review in NTRK fusion cancer patients previously treated with TRK inhibitor [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks while on treatment, and every 12 weeks after the last dose (for up to 2 years) in patients who have not progressed ]
    For Phase 1

  7. Best overall response of confirmed CR or PR as determined by treating investigators using RANO in patients with primary CNS malignancies. [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks while on treatment, and every 12 weeks after the last dose (for up to 2 years) in patients who have not progressed ]
    For Phase 1

  8. Characterize PK properties of Loxo-195 [ Time Frame: Days 1 and 8 of Cycle 1 and Day 1 of Cycles 3 and 5; additional timepoints for intrapatient dose escalation ]
    For Phase 1

  9. Best overall response of confirmed PR or CR using RECIST v1.1 or RANO criteria as appropriate in patients with documented NTRK fusion cancers, who discontinued previous TRK inhibitor due to intolerance [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks while on treatment, and every 12 weeks after the last dose (for up to 2 years) in patients who have not progressed ]
    For Phase 2

  10. Duration or response (DOR) for patients with best overall response of confirmed CR or PR by an independent radiology review committee [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks while on treatment, and every 12 weeks after the last dose (for up to 2 years) in patients who have not progressed ]
    For Phase 2

  11. Duration or response (DOR) for patients with best overall response of confirmed CR or PR by the treating Investigator [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks while on treatment, and every 12 weeks after the last dose (for up to 2 years) in patients who have not progressed ]
    For Phase 2

  12. Progression-free survival (PFS) [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks while on treatment, and every 12 weeks after the last dose (for up to 2 years) in patients who have not progressed ]
    For Phase 2

  13. Overall survival (OS) [ Time Frame: Up to 24 months ]
    For Phase 1 and Phase 2

  14. Clinical benefit rate (CBR) [ Time Frame: Up to 24 months ]
    For Phase 2



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Advanced solid tumor for which, in the opinion of the Investigator, no other standard or investigational therapy offers greater benefit.
  • A solid tumor diagnosis in the setting of:

    1. a documented NTRK fusion and a clinical history of relapse following a response to a prior TRK inhibitor
    2. a documented NTRK fusion unresponsive to a prior TRK inhibitor
    3. a documented NTRK fusion and a clinical history of intolerance to a prior TRK inhibitor
  • NTRK gene fusions will be identified via a CLIA certified (or equivalent) laboratory. Exception: Patients with Infantile Fibrosarcoma (IFS) and congenital mesoblastic nephroma (CMN) may be enrolled based on ETV6+ FISH test without identifying NTRK3
  • Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 3 (age ≥16) or Lansky Performance Score (LPS) ≥40% (age<16). If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky Performance Status (KPS) (age ≥16) or LPS (age<16) ≥ 50%
  • Life expectancy > 4 weeks
  • Adequate hematologic, hepatic and renal function.
  • Patients with stable CNS primary tumor, brain metastases, or treated spinal cord compression are eligible if neurological symptoms and steroid use (if applicable) have been stable for 7 days prior to the first dose of LOXO-195
  • Ability to receive study drug therapy by enteral administration

Key Exclusion Criteria:

  • Required treatment with certain strong CYP3A4 inhibitors or inducers.
  • Clinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of LOXO-195 or prolongation of the QT interval corrected (QTcF) > 480 msec within the past 6 months
  • Major surgery within 7 days of enrollment
  • Uncontrolled systemic bacterial, fungal or viral infection
  • Pregnancy or lactation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03215511


Contacts
Contact: Patient Advocacy 1-855-NTRK-123 clinicaltrials@loxooncology.com

Locations
United States, California
Stanford Cancer Center Recruiting
Stanford, California, United States, 94304
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Loxo Oncology, Inc.
Bayer
Investigators
Study Director: Nora Ku, MD Senior Medical Director, Loxo Oncology

Responsible Party: Loxo Oncology, Inc.
ClinicalTrials.gov Identifier: NCT03215511     History of Changes
Other Study ID Numbers: LOXO-EXT-17005
First Posted: July 12, 2017    Key Record Dates
Last Update Posted: March 1, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Loxo Oncology, Inc.:
NTRK Fusion Positive
LOXO-195
Loxo
TRK
TRK Fusion
NTRK1
NTRK2
NTRK3
TRKA
TRKB
TRKC
NTRK
ETV6
fusion
tumors
CNS tumors
solid tumors
central nervous system tumors
advanced cancer
primary CNS tumor
Advanced CNS tumor
Metastatic CNS tumor
NTRK1 fusion
NTRK2 fusion
NTRK3 fusion
ETV6-NTRK3
ETV6 fusion
Metastatic cancer
Cancer of Unknown Primary Site
Pediatric

Additional relevant MeSH terms:
Carcinoma
Neoplasms
Melanoma
Carcinoma, Squamous Cell
Glioblastoma
Thyroid Diseases
Astrocytoma
Thyroid Neoplasms
Cholangiocarcinoma
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Head and Neck Neoplasms
Lung Neoplasms
Pancreatic Neoplasms
Ovarian Neoplasms
Brain Neoplasms
Carcinoma, Renal Cell
Nervous System Neoplasms
Central Nervous System Neoplasms
Fibrosarcoma
Nerve Sheath Neoplasms
Neurofibroma
Neurilemmoma
Neurofibrosarcoma
Uterine Neoplasms
Biliary Tract Neoplasms
Thoracic Neoplasms
Intestinal Neoplasms
Respiratory Tract Neoplasms
Carcinoma, Bronchogenic