A Study to Test the Safety of the Investigational Drug Selitrectinib in Children and Adults That May Treat Cancer

This research study is done to test the safety of the new drug selitrectinib in children and adults with cancer having a change in a particular gene (NTRK1, NTRK2 or NTRK3). The drug may treat cancer by interfering with the effect of the NTRK genes on cancer growth. The study also investigates how the drug is absorbed and processed in the human body, and how well and for how long the cancer responds to the drug. This is the first study to test selitrectinib in humans with cancer, for whom no other effective therapy exists.

Inclusion Criteria

• 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) 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 equivalently-accredited diagnostic) laboratory. If such a report cannot be provided, other available certifications/accreditations are required and need to be documented. 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 ≤ 2 in adults or Karnofsky Performance Score (KPS) Score≥50% (age ≥ 16 years) or Lansky Performance Score (LPS) ≥ 40% (age < 16 years). - Life expectancy of at least 3 months. - Adequate hematologic, hepatic and renal function. - Patients with stable central nervous system (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 selitrectinib. - Ability to receive study drug orally or by enteral administration Exclusion Criteria: - Prior exposure to second generation TRK inhibitor (e.g. selitrectinib, repotrectinib (TPX-0005)), taletrectinib (DS-6501b/AB-106)). Exception is in case patient presented intolerance to the second generation TRK inhibitor agent and the duration of exposure was less than 28 days. No previous treatment with selitrectinib is allowed. - Concurrent treatment with a strong CYP3A4 inhibitor or inducer, consumption of grapefruit juice or Seville oranges, or drugs associated with QT prolongation. - Clinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of selitrectinib, 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 selitrectinib or Ora-Sweet® SF and OraPlus® for patients receiving liquid formulation.

The trial will be conducted in 2 parts: dose escalation and expansion (Phase 1) and Phase 2.

The primary objective of Phase 1 is to establish the recommended dose of selitrectinib 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 radiology committee (IRR). Secondary objectives of

Phase 2 comprise the safety and efficacy of selitrectinib at the recommended dose.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Bayer Corporation

• Primary ID 20810
• Secondary IDs NCI-2017-01629, 2017-004246-20, LOXO-EXT-17005
• Clinicaltrials.gov ID NCT03215511