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

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.

Conducting Institutions:

Massachusetts General Hospital, Children's Hospital Boston, Dana-Farber Cancer Institute

Overall PI:

Site-responsible Investigators:

Contacts:

Eligibility 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.