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

Status: Active


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.

Eligibility Criteria

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:
  • a documented NTRK fusion and a clinical history of relapse following a response to a prior TRK inhibitor
  • a documented NTRK fusion unresponsive to a prior TRK inhibitor
  • 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

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

Locations & Contacts


Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: In review
Contact: Amanda Gonzales
Phone: 310-794-3908
Palo Alto
Stanford Cancer Institute Palo Alto
Status: Active
Contact: Cancer Clinical Trials Office
Phone: 650-498-7061
San Diego
University of California San Diego
Status: Active
Name Not Available


Dana-Farber Cancer Institute
Status: Approved
Name Not Available
Massachusetts General Hospital Cancer Center
Status: Active
Name Not Available


Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: Approved
Name Not Available

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Name Not Available


OHSU Knight Cancer Institute
Status: Active
Name Not Available


St. Jude Children's Research Hospital
Status: Active
Name Not Available


UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Contact: Marcella West Aguilar
Phone: 214-648-1479
M D Anderson Cancer Center
Status: Active
Name Not Available


Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Name Not Available


Fred Hutch / University of Washington Cancer Consortium
Status: Active
Name Not Available

Trial Objectives and Outline

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.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type


Lead Organization

Lead Organization
Bayer Corporation

Trial IDs

Primary ID 20810
Secondary IDs NCI-2017-01629, LOXO-EXT-17005 ID NCT03215511