Patient case: 60-year-old male with melanoma; genetic feature: NTRK1 rearrangement

Clinical trial: Study of LOXO-101 in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE)

Summary: Phase II, multi-center, open-label study of patients with advanced solid tumors harboring a fusion of NTRK1, NTRK2 or NTRK3.

Detailed description: This is a Phase II, multi-center, open-label study of patients with advanced solid tumors harboring a fusion of NTRK1, NTRK2 or NTRK3. Patients with NTRK1, NTRK2 or NTRK3 fusion-positive cancers will be identified through molecular assay.
  LOXO-101 will be administered at 100mg twice daily (BID), with each cycle consisting of 28 days of dosing administered on a continuous basis.
  The study will include 8 cohorts of patients with tumors bearing NTRK fusions, including non small cell lung cancer, thyroid cancer, sarcoma, colorectal cancer, salivary gland cancer, biliary cancer and primary CNS tumor, as well as a cohort that will enroll patients not included in the histologies listed above.

Eligibility: Key Inclusion Criteria:
  1. Locally-advanced or metastatic malignancy with an NTRK1, NTRK2 or NTRK3 gene fusion, identified through molecular assays as routinely performed at CLIA or other similarly-certified laboratories.
  2. Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy.
  3. Subjects must have at least one measurable lesion as defined by RECIST 1.1 (Eisenhauer 2009). Subjects without RECIST measurable disease (e.g., evaluable disease only) will be eligible for enrollment to Cohort 8, regardless of tumor type. Subjects in Cohort 7 (primary CNS tumors) should meet the following criteria:
  -  Have received prior treatment including radiation and/or chemotherapy, with radiation completed > 12 weeks prior to C1D1 of therapy.
  -  Have ≥ 1 site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging [MRI] and evaluable by RANO criteria), with the size of at least one of the measurable lesions ≥ 1 cm in each dimension and noted on more than one imaging slice.
  -  Imaging study performed within 28 days before enrollment while on stable dose steroid medication for at least 5 days immediately before and during the imaging study.
  4. Adequate organ function as defined by the following criteria:
  -  Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) < 2.5 upper limit of normal (ULN), or AST and ALT < 5 ULN if liver function abnormalities are due to underlying malignancy.
  -  Total bilirubin < 2.0 ULN. Subjects with a known history of Gilberts Disease and an isolated elevation of indirect bilirubin are eligible.
  -  Serum creatinine < 2.0 ULN OR an estimated glomerular filtration rate ≥ 30 mL/minute using the Cockroft-Gault formula.
  5. Ability to swallow capsules,
  Key Exclusion Criteria:
  1. Symptomatic or unstable brain metastases. (Note: Subjects with asymptomatic brain metastases are eligible to participate in the study). Subjects with primary CNS tumors are eligible.
  2. Pregnancy or lactation.

Relevance to patient case: not relevant