LOXO-EXT-17005: A Phase 1/2 Study of the TRK Inhibitor LOXO-195 in Adult and Pediatric Subjects with Previously Treated NTRK Fusion Cancers
Study ID: STU 112017-078
The trial will be conducted in 2 parts: dose escalation (Phase I ) and dose expansion (Phase 2) .
The primary objective of Phase 1 is to establish the recommended dose of Loxo-195 to treat neurotrophic tyrosine kinase (NTRK) fusion cancers in patients a) aged 12 years and older and b) younger than 12 years. Secondary objectives of Phase 1 are to characterize the pharmakokinetic properties of the test drug, its safety and tolerability, and to assess the objective response rate (ORR) of NTRK-tumors.
The primary objective of Phase 2 is to assess the overall response rate in NTRK fusion cancer patients as determined by an independent review committee (IRC). Secondary objectives of Phase 2 comprise the safety and efficacy of Loxo-195 at the recommended dose.
- 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) a documented NTRK fusion and a clinical history of relapse following a response to a prior TRK inhibitor
- b) a documented NTRK fusion unresponsive to a prior TRK inhibitor
- c) a documented NTRK fusion and a clinical history of intolerance to a prior TRK inhibitor
- NTRK gene fusions will be identified in a CLIA-certified (or equivalent) laboratory. Patients with infantile fibrosarcoma (IFS) or congenital mesoblastic nephroma (CMN) may be enrolled based on an ETV6+ FISH test without identifying NTRK3
- Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 3 (age ≥ 16 years) or Lansky Performance Score (LPS) ≥ 40% (age < 16 years). If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky Performance Score (KPS) (age ≥ 16 years) or LPS (age < 16 years) ≥ 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 have been stable for 7 days prior to the first dose of LOXO-195
- Ability to receive study drug orally or by enteral administration
- Concurrent treatment with a strong CYP3A4 inhibitor or inducer or drugs associated with QT prolongation.
- Clinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of LOXO-195, or prolongation of QT interval corrected for heart rate (QTc interval) >480 milliseconds within past 6 months
- Major surgery within 7 days of enrollment
- Uncontrolled systemic bacterial, fungal or viral infection.
- Pregnancy or lactation.
- Known hypersensitivity to LOXO-195 or Ora-Sweet® SF and OraPlus® for patients receiving liquid formulation.
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Theodore W Laetsch
LOXO ONCOLOGY INC
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