Phase 1 / 2 Multicenter Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of APL-101 in Subjects With Non-Small Cell Lung Cancer With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advance Solid Tumors
Brief SummaryThe primary Phase 1 purpose of this study is to assess overall safety and tolerability and recommended Phase 2 dose (RP2D) of APL-101. The Phase 2 portion will assess efficacy of the dose determined in phase 1 in individuals with Non-Small Cell Lung Cancer with c-Met EXON 14 skip mutations and c-Met Dysregulation Advance Solid Tumors
Detailed DescriptionThis is a Phase 1, multi-center, open-label, 2-part study with a Dose Escalation Segment and Dose and Disease Expansion Cohorts study of APL-101, a c-MET inhibitor, to determine the recommended Phase 2 dose (RP2D) and dose limiting toxicities for APL-101, and to obtain preliminary efficacy and target engagement data, in subjects with NSCLC and advanced malignancies with c-Met dysregulation. c-MET dysregulation will be determined from historical results by molecular pre-screening evaluations to determine eligibility of enrollment for both the Dose Escalation Segment and Dose and Disease Expansion Cohorts. However, in the Dose and Disease Expansion Cohorts, the c-MET historical results will be confirmed by a central laboratory retrospectively, but will not be a determinant for study entry. Dose escalation will occur until a protocol defined dose limited toxicity (DLT) occurs and a tentative maximum tolerated dose (MTD) is determined. Once dose is determined, three cohort groups will be further evaluated: Cohort A: EXON 14 NSCLC (c-Met naïve), Cohort B: EXON 14 NSCLC (c-Met experienced; progressed on prior c-Met inhibitor), Cohort C: basket of tumor types with c-Met dysregulation (amplification or mutation or fusions)
Inclusion and Exclusion 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 locally advanced, recurrent or relapsed or metastatic incurable solid malignancy - For Phase 2, three cohorts will be enrolled: Cohort A: EXON 14 NSCLC (c-Met naïve), Cohort B: EXON 14 NSCLC (c-Met experienced; progressed on prior c-Met inhibitor), Cohort C: basket of tumor types with c-Met dysregulation (amplification or mutation or fusions).
- 7. - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. - No planned major surgery within 4 weeks of first dose of APL-101 Major
- Hypersensitivity to CBT-101, excipients of the drug product, or other components of the study treatment regimen.
- Known mutation of EGFR, ALK or ROS1 or have received a kinase inhibitor for these mutations
- History of, or at risk for, cardiac disease (e.g., long QTc syndrome [> 450 msec] or concurrent treatment with any medication that prolongs QT interval).
- Symptomatic primary tumors or metastasis of brain and/or central nervous system, uncontrolled with antiepileptic and requiring high doses of steroids.
- 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.
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