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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

Description

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. 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.

Status

Accepting new patients

Primary Study Objective(s)

The primary objective for phase 1 of this study is:

  • Maximum Tolerated Dose (MTD)
  • Recommended dose for further study in patients age 12 and older and age <12

The primary objective of phase 2 is:

  • Best overall response of confirmed Partial Response or Complete Response 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.

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who have:

  • 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, who are eligible if neurological symptoms and steroid use (if applicable) have been stable for seven days prior to the first dose of LOXO-195
  • Ability to receive study drug orally or by enteral administration

Excluding patients who:

  • Are required to have treatment with certain strong CYP3A4 inhibitors or inducers
  • Have clinically significant active cardiovascular disease or history of myocardial infarction within three months prior to planned start of LOXO-195 or prolongation of the QT interval corrected (QTcF) > 480 msec within the past six months
  • Have had major surgery within seven days of enrollment
  • Have an uncontrolled systemic bacterial, fungal or viral infection
  • Are pregnant or lactating
  • Have a known hypersensitivity to any of the components of LOXO-195 or Ora-Sweet® SF and OraOlus, for patients receiving liquid suspension