APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors

For people ages 18 years and up

Major Inclusion Criteria:

• Able to understand and comply with study procedures, understand the risks involved, and provide written informed consent.
• For Phase 1, histologically and / or cytological confirmed unresectable or metastatic solid malignancy, refractory to standard therapies with no more than three prior lines of therapy.
• For Phase 2, five cohorts will be enrolled: Cohort A-1: NSCLC EXON 14 skip mutation (c-Met naïve) for first line treatment, Cohort A-2: NSCLC EXON 14 skip mutation (c-Met naïve) pretreated subjects with no more than 3 lines of prior therapy, Cohort B: NSCLC EXON 14 skip mutation (c-Met experienced; radiographic progression on prior c-Met inhibitor), Cohort C: basket of tumor types with c-Met high level amplification (NSCLC

EXON 14 skip mutation excluded), Cohort D: basket of tumor type with c-Met fusions.

• Local/archival result (tissue and/or plasma) of a positive c-Met dysregulation is required
• Measurable disease according to RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• No chemotherapy treatments within at least 3 weeks prior to first dose of study treatment
• No planned major surgery within 4 weeks of first dose of APL-101

Major Exclusion Criteria:

• Hypersensitivity to APL-101, excipients of the drug product, or other components of the study treatment regimen.
• Known mutation/gene rearrangement of EGFR (except for Cohort C), ALK, ROS1, RET, NTRK, KRAS, and BRAF.
• History of, or currently, or at risk for, cardiac disease (e.g., long QT syndrome [> 450 msec QTcF or concurrent treatment with any medication that prolongs QT interval).
• Unable to swallow orally administered medication whole.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., Crohn's, ulcerative colitis, active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
• Women who are breastfeeding.