The 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
This 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, four 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 high-level amplifications), Cohort D:
basket of tumor types (with c-Met fusions)
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 locally advanced, recurrent
or relapsed or metastatic incurable solid malignancy
- For Phase 2, four 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 high amplification, Cohort D: basket of
tumor types with c-Met fusions.
- Local/archival result (tissue and/or plasma) of a positive c-Met dysregulation is
- Measurable disease according to RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- 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, ALK, ROS1, RET, NTRK, KRAS, BRAF or other
driver mutation/gene rearrangement apart from MET
- History of, 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
- Women who are breastfeeding.