Active, currently enrolling
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
NCT No.: NCT03175224
Study Type: INTERVENTIONAL
Phase:
Phase II
Region: California - Northern
Acronym: (SPARTA)
Official Title
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
Purpose
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 Advance Solid Tumors.
Detailed Description
This 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).
Age Limit
18 years & older
Eligibility Criteria
Inclusion Criteria
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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)
Measurable disease according to RECIST v1.1. 7.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
No planned major surgery within 4 weeks of first dose of APL-101
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Exclusion Criteria
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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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Keywords and/or Specific Medical Conditions
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Neoplasms by Histologic Type
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Neoplasms, Glandular and Epithelial
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Respiratory Tract Diseases
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Respiratory Tract Neoplasms
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Sponsors
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