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 Advanced 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 Advanced Solid Tumors
Detailed DescriptionThis is a Phase 1/2, multi-center, global, 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 (Phase 1) and Dose and Disease Expansion Cohorts (Phase 2). 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, five cohort groups will be further evaluated: - Cohort A-1: NSCLC EXON 14 skip mutation (c-Met naïve, 1L) - Cohort A-2: NSCLC EXON 14 skip mutation (c-Met naïve, 2/3L), - Cohort B: NSCLC EXON 14 skip mutation (c-Met experienced; progressed on prior c-Met inhibitor), - Cohort C: basket of tumor types (with c-Met high-level amplifications), - Cohort D: basket of tumor types (with c-Met 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 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
- 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.
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.