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

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.

Key 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:

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 orally or 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.

- Known hypersensitivity to any of the components of LOXO-195 or Ora-Sweet® SF and
OraOlus, for patients receiving liquid suspension