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 was to assess overall safety, 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; individuals with cancers associated with c-Met amplifications; individuals with cancers associated with c-Met fusion

Trial Description

Primary Outcome:

  • Estimate the maximum tolerated dose (MTD) and the incidence of DLTs in Phase 1
  • Objective response rate (ORR = CR + PR) per blinded independent review committee (BIRC) based on RECIST v1.1 (or relevant criteria per tumour type)
Secondary Outcome:
  • Median duration of response (DOR) per BIRC.
  • ORR per investigator assessment based on RECIST v1.1.
  • Median DOR per investigator assessment.
  • Antitumour activity by clinical benefit rate (CR + PR + SD ≥ 4 cycles) based on RECIST v1.1 Median time to progression (TTP).
  • Median time to progression (TTP).
  • Progression Free Survival (PFS) and overall survival (OS) at 6, 12, 18 and 24 months
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

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Resources

Canadian Cancer Society

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