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

Official Title

Phase 1 / 2 Multicentre 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 Tumours

Summary:

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 Tumours

Trial Description

Primary Outcome:

• Estimate the maximum tolerated dose (MTD) and the incidence of DLTs
• Determine response rate in Phase 2

Secondary Outcome:

• Incidence of SAE and AEs
• Area under the plasma concentration versus time curve (AUC)
• Maximum plasma concentration
• Time to reach Cmax
• Duration of Response
• Progression Free Survival
• Overall Survival

This is a Phase 1/2, multi-centre, 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 tumour types (with c-Met high-level amplifications),

• Cohort D: basket of tumour types (with c-Met fusions)

View this trial on ClinicalTrials.gov