Clinical Trials /

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

NCT03175224

Description:

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

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
  • 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 Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: APL-101-01 (CBT-101-01)
  • NCT ID: NCT03175224

Conditions

  • Solid Tumor
  • Advanced Cancer
  • Renal Cancer
  • Gastric Cancer
  • Gastroesophageal Junction Adenocarcinoma
  • NSCLC
  • Lung Cancer

Interventions

DrugSynonymsArms
APL-101 Oral CapsulesPLB-1001, CBI-3103, Bozitinib, CBT-101Single-Arm

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 Advanced Solid Tumors

Detailed Description

      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)
    

Trial Arms

NameTypeDescriptionInterventions
Single-ArmExperimentalAPL-101 Oral Capsules
  • APL-101 Oral Capsules

Eligibility Criteria

        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
             required

          -  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
             syndrome).

          -  Women who are breastfeeding.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Estimate the maximum tolerated dose (MTD) and the incidence of DLTs
Time Frame:From the time of informed consent signature through Cycle 1 (28 days) completion
Safety Issue:
Description:Adverse events, serious adverse events, and dose limiting toxicities

Secondary Outcome Measures

Measure:Incidence of SAE and AEs
Time Frame:Approximately 1 year
Safety Issue:
Description:Adverse events, serious adverse events, and dose limiting toxicities according to the National Cancer Institute (NCI) Terminology Criteria for Adverse Events (CTCAE v4.03)
Measure:Area under the plasma concentration versus time curve (AUC)
Time Frame:Up to 2 months (1 cycle = 28 days)
Safety Issue:
Description:AUC, 0 - infinity
Measure:Maximum plasma concentration
Time Frame:Up to 2 months (1 cycle = 28 days)
Safety Issue:
Description:Cmax
Measure:Time to reach Cmax
Time Frame:Up to 2 months (1 cycle = 28 days)
Safety Issue:
Description:Tmax
Measure:Duration of Response
Time Frame:Approximately 24 months
Safety Issue:
Description:Anti-tumor activity per RECIST v1.1
Measure:Progression Free Survival
Time Frame:Approximately 24 months
Safety Issue:
Description:Anti-tumor activity per RECIST v1.1
Measure:Overall Survival
Time Frame:Approximately 24 months
Safety Issue:
Description:Anti-tumor activity per RECIST v1.1

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Apollomics Inc.

Trial Keywords

  • Advanced Solid Tumor
  • Relapsed Solid Tumor
  • Recurrent Solid Tumor

Last Updated

December 18, 2019