Clinical Trial - NCT03215511

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

Recruiting

Sponsor: Loxo Oncology, Inc.

Collaborators: Bayer

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03215511

Protocol Info

Short Description: Phase 1/2 of LOXO-195 in NTRK Fusion or Non-Fusion NTRK Altered Cancers
Long Description: A Phase 1/2 Study of the TRK Inhibitor LOXO-195 in Adult and Pediatric Subjects with Previously Treated NTRK Fusion Cancers
MGH Status: Open
Sponsor: Loxo Oncology Inc.
Disease Program: Phase I

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

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 Title Intervention 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 LOXO-195 Phase 1/Phase 2
Study Type Interventional
Official Title A Phase 1/2 Study of the TRK Inhibitor LOXO-195 in Adult and Pediatric Subjects With Previously Treated NTRK Fusion Cancers

Primary Outcome Measures

Maximum Tolerated Dose (MTD) [Time Frame: The first 28 days of treatment (Cycle 1)] [Designated as safety issue: ]

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)] [Designated as safety issue: ]

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] [Designated as safety issue: ]


Secondary Outcome Measures

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)] [Designated as safety issue: ]

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)] [Designated as safety issue: ]

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)] [Designated as safety issue: ]

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)] [Designated as safety issue: ]

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)] [Designated as safety issue: ]

Overall response as assessed by RECIST v1.1 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] [Designated as safety issue: ]

Overall response of confirmed CR or PR as determined by treating investigator 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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Overall response using RECIST v1.1 of confirmed CR or PR by independent radiology review in NTRK fusion cancer patients 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] [Designated as safety issue: ]

Overall response of confirmed CR or PR as determined by treating investigators using RECIST v1.1 or RANO 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] [Designated as safety issue: ]

Overall response of confirmed CR or PR as determined by treating investigators using RECIST v1.1 or RANO in NTRK fusion cancer patients 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] [Designated as safety issue: ]

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 in patients who have not progressed] [Designated as safety issue: ]

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 in patients who have not progressed] [Designated as safety issue: ]

Progression-free survival (PFS) as determined by independent radiology review [Time Frame: Approximately every 8 weeks for one year, then every 12 weeks while on treatment and every 12 weeks after the last dose in patients who have not progressed] [Designated as safety issue: ]

Progression-free survival (PFS) as determined by 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 in patients who have not progressed] [Designated as safety issue: ]

Overall survival (OS) [Time Frame: Up to 24 months] [Designated as safety issue: ]

Clinical benefit rate (CBR) as determined by independent radiology review [Time Frame: Up to 24 months] [Designated as safety issue: ]

Clinical benefit rate (CBR) as determined by 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 in patients who have not progressed] [Designated as safety issue: ]

Estimated Enrollment: 93
Study Start Date: July 2017
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: August 2019
Arms Assigned Interventions

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

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Key Inclusion Criteria:

  • Advanced solid tumor for which, in the opinion of the Investigator, no other standard 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 orally or 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.
  • Known hypersensitivity to any of the components of LOXO-195 or Ora-Sweet® SF and OraOlus, for patients receiving liquid suspension

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03215511

Locations

  • United States, California
    • University of California, San Diego (UCSD) - Moores Cancer Center La Jolla, California, United States, 92093
    • University of California, Los Angeles Los Angeles, California, United States, 90095
    • Stanford Cancer Center Stanford, California, United States, 94304
  • United States, Colorado
    • Sarah Cannon Research Institute at HealthONE Denver, Colorado, United States, 80218
  • United States, Illinois
    • Cancer Treatment Centers of America (CTCA) - Midwestern Regional Medical Center Zion, Illinois, United States, 60099
  • United States, Louisiana
    • Ochsner Clinic Foundation New Orleans, Louisiana, United States, 70121
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02115
  • United States, New York
    • Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065
  • United States, Oregon
    • Oregon Health and Science University Portland, Oregon, United States, 97239
  • United States, Pennsylvania
    • Children's Hospital of Philadelphia- Center for Childhood Cancer Research Philadelphia, Pennsylvania, United States, 19104
    • Cancer Treatment Centers of America (CTCA) - Eastern Regional Medical Center Philadelphia, Pennsylvania, United States, 19124
  • United States, Tennessee
    • St. Jude Children's Research Hospital, Inc. Memphis, Tennessee, United States, 38105
    • Sarah Cannon Research Institute Nashville, Tennessee, United States, 37203
  • United States, Texas
    • University of Texas, Southwestern Medical Center Dallas, Texas, United States, 75235
    • MD Anderson Cancer Center Houston, Texas, United States, 77030
  • United States, Virginia
    • Virginia Oncology Associates Norfolk, Virginia, United States, 23502
  • United States, Washington
    • Seattle Children's Seattle, Washington, United States, 98105
  • Australia, New South Wales
    • Sydney Children's Hospital, Kids Cancer Centre Randwick, New South Wales, Australia, 2031
  • Denmark,
    • Righospitalet Copenhagen, , Denmark, 2100
  • France,
    • Gustave Roussy Villejuif cedex, , France, 94805
  • Italy, MI
    • Fondazione IRCCS Istituto Nazionale dei Tumori Milano, MI, Italy, 20133
  • Korea, Republic of,
    • Seoul National University Hospital Seoul, , Korea, Republic of, 03080
  • Singapore,
    • National Cancer Centre Singapore Singapore, , Singapore, 169601
  • Spain,
    • Hospital Universitario Vall d'Hebron Barcelona, , Spain, 08035
    • Hospital Vall d'Hebron Madrid, , Spain, 28036
    • Fundacion Jimenez Diaz Madrid, , Spain, 28040

Sponsors and Collaborators

Loxo Oncology, Inc.

Bayer

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03215511
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

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

NTRK1 gene rearrangement

NTRK2 gene rearrangement

NTRK3 gene rearrangement

ETV6 gene rearrangement

NTRK gene rearragements

Congenital Nephroma

Metastatic Infantile Fibrosarcoma

Advanced Infantile Fibrosarcoma

Additional relevant MeSH terms:

Carcinoma

Neoplasms

Melanoma

Carcinoma, Squamous Cell

Glioblastoma

Thyroid Diseases

Astrocytoma

Thyroid Neoplasms

Cholangiocarcinoma

Carcinoma, Non-Small-Cell Lung

Squamous Cell Carcinoma of Head and Neck

Colorectal Neoplasms

Lung Neoplasms

Pancreatic Neoplasms

Ovarian Neoplasms

Brain Neoplasms

Carcinoma, Renal Cell

Nervous System Neoplasms

Central Nervous System Neoplasms

Nerve Sheath Neoplasms

Fibrosarcoma

Neurofibrosarcoma

Uterine Neoplasms

Biliary Tract Neoplasms

Thoracic Neoplasms

Intestinal Neoplasms

Respiratory Tract Neoplasms

Bronchial Neoplasms

Carcinoma, Bronchogenic

Bile Duct Neoplasms

Neoplasms, Nerve Tissue

Nephroma, Mesoblastic

Nevi and Melanomas

Salivary Gland Neoplasms

9-Fluoro-15-methyl-2,11,16,20,21,24-hexaazapentacyclo(16.5.2.02,6.07,12.021,25)pentacosa-1(24),7,9,11,18(25),19,22-heptaen-17-one

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019