Clinical Trials /

First-in-human Phase I Study of a Selective c-Met Inhibitor PLB1001

NCT02896231

Description:

This phase I, first-in-human dose-escalation study was conducted to determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), dose-limiting toxicities (DLTs), pharmacokinetics (PK) profile, and preliminary antitumor activity of PLB1001.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First-in-human Phase I Study of a Selective c-Met Inhibitor PLB1001
  • Official Title: A Phase I Open-label, Multicenter Dose Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of PLB1001 in Patients With Met-positive (Met+) Advanced Non-small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: HMO-PLB1001-2013012-01
  • NCT ID: NCT02896231

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
PLB1001BozitinibPLB1001

Purpose

This phase I, first-in-human dose-escalation study was conducted to determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), dose-limiting toxicities (DLTs), pharmacokinetics (PK) profile, and preliminary antitumor activity of PLB1001.

Detailed Description

      This is a Phase I, open-label, multicentre study of PB1001 administered orally to patients
      with Met-positive (Met+) advanced NSCLC. The study includes a Dose-escalation Part (part
      A)and a Dose Expansion Part(part B). The aim of the part A is to estimate the MTD and to
      identify the dose limited toxicity(DLT) and the recommended phase II dose (RP2D) for PLB1001
      single agent as well as to determine the PK/PD profile .Once response has been observed in
      certain dose level ,then followed by the expansion part to further assess the clinical
      efficacy and safety of PLB1001 single agent. Aprox. 40 patients will be enrolled in PART A,
      while 20-30 patients for expansion cohort .

      PLB1001 is a potent selective c-Met inhibitor. PLB1001 acts on cancer by blocking abnormal
      cmet-mediated signalling, leading to profound tumour growth inhibition in xenografts of
      non-small cell lung cancer (NSCLC) tumours. Preliminary data from a c-Met inhibitor INC 280
      has provided possibility on the safety and clinical activity of PLB1001 monotherapy in this
      patient population.
    

Trial Arms

NameTypeDescriptionInterventions
PLB1001ExperimentalThere are 5 dose cohorts, including 50mg BID, 100mg BID, 150mg BID, 200mg BID and 275mg BID in the dose escalation stage and PLB1001 will be administered orally to patients twice daily for each dose cohort.
  • PLB1001

Eligibility Criteria

        Inclusion Criteria:

          -  Signed Informed Consent Form

          -  Age≥18 years

          -  Histologically or cytologically confirmed advanced non-small cell lung cancer

          -  Must have evidence of c-Met positivity from the results of molecular pre-screening
             evaluations

          -  At least one measurable lesion as per RECIST v1.1

          -  Patients must have recovered from all toxicities related to prior anticancer therapies
             to grade ≤ 1

          -  ECOG Performance Status of 0-2

        Exclusion Criteria:

          -  Previous or current treatment with a c-Met inhibitor or HGF-targeting therapy

          -  Symptomatic central nervous system (CNS) metastases that are neurologically unstable
             or requiring increasing doses of steroids to control, and patients with any CNS
             deficits.

          -  Clinically significant, uncontrolled heart diseases. Unstable angina History of
             documented congestive heart failure (New York Heart Association functional
             classification > II) Uncontrolled hypertension defined by a Systolic Blood Pressure
             (SBP) ≥ 140 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 90 mm Hg Arrhythmias

          -  Active peptic ulcer disease or gastritis

          -  Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1,
             except for alopecia

          -  Major surgery within 4 weeks prior to starting PLB1001

          -  Previous anti-cancer and investigational agents within 4 weeks before first dose of
             PLB1001. If previous treatment is a monoclonal antibody, then the treatment must be
             discontinued at least 6 weeks before first dose of PLB1001.

          -  Pregnant or nursing women

          -  Involved in other clinical trials < 30 days prior to Day 1
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of participants with dose-limiting toxicities
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Area under the plasma concentration versus time curve (AUC) of PLB1001 and its metabolite
Time Frame:Day 1-2 Single Dose and Day 1-28 Steady State
Safety Issue:
Description:In the study of single-dose, full Pharmacokinetics (PK) profiles ofPLB1001 will be obtained following administration of a single oral dose of PLB-1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics (PK) sampling will include a pre-dose and at the 0.5, 2, 4, 6, 8, 10, 10.5, 12 and 13 hour time points on days 8, 22of dosing in the first 28-Day cycle of therapy, and pre-dose on days 9, 14, 15, 16and 23 of the first 28-Day cycle of therapy
Measure:Maximum plasma concentration observed (Cmax) of PLB1001 and its metabolite
Time Frame:Day 1-2 Single Dose and Day 1-28 Steady State
Safety Issue:
Description:In the study of single-dose, full Pharmacokinetics (PK) profiles ofPLB1001 will be obtained following administration of a single oral dose of PLB-1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics (PK) sampling will include a pre-dose and at the 0.5, 2, 4, 6, 8, 10, 10.5, 12 and 13 hour time points on days 8, 22of dosing in the first 28-Day cycle of therapy, and pre-dose on days 9, 14, 15, 16and 23 of the first 28-Day cycle of therapy
Measure:Time to Cmax (Tmax) of PLB1001 and its metabolite
Time Frame:Day 1-2 Single Dose and Day 1-28 Steady State
Safety Issue:
Description:In the study of single-dose, full Pharmacokinetics (PK) profiles ofPLB1001 will be obtained following administration of a single oral dose of PLB-1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics (PK) sampling will include a pre-dose and at the 0.5, 2, 4, 6, 8, 10, 10.5, 12 and 13 hour time points on days 8, 22of dosing in the first 28-Day cycle of therapy, and pre-dose on days 9, 14, 15, 16and 23 of the first 28-Day cycle of therapy
Measure:Preliminary antitumor activity of PLB1001
Time Frame:2 years
Safety Issue:
Description:Preliminary antitumor activity of PLB1001 assessed using RECIST1.1

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Beijing Pearl Biotechnology Limited Liability Company

Last Updated

October 10, 2017