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.

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

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.

Lead Organization
Bayer Corporation