Clinical Trials /

Phase I Study of a Selective ALK Inhibitor PLB1003 in Patients With ALK+ NSCLC.

NCT03130881

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 PLB1003.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Study of a Selective ALK Inhibitor PLB1003 in Patients With ALK+ NSCLC.
  • Official Title: A Phase I Open-label, Multicenter Dose Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of PLB1003 in Patients With ALK-positive (ALK+) Advanced Non-small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: HMO-PLB1003-20160828
  • NCT ID: NCT03130881

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
PLB1003PLB1003

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 PLB1003.

Detailed Description

      This is a Phase I, open-label study of PB1003 administered orally to patients with
      ALK-positive (ALK+) 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 PLB1003 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 PLB1003 single agent. Aprox 40 patients will be enrolled in PART A, while 12-24
      patients for expansion cohort .

      PLB1003 is a potent selective ALK inhibitor. PLB1003 acts on cancer by blocking abnormal
      ALK-mediated signaling, leading to profound tumour growth inhibition in xenografts of
      non-small cell lung cancer (NSCLC) tumours.
    

Trial Arms

NameTypeDescriptionInterventions
PLB1003ExperimentalALK-positive (ALK+) advanced NSCLC
  • PLB1003

Eligibility Criteria

        Inclusion Criteria:

          -  Signed Informed Consent Form

          -  Age≥18 years

          -  Diagnosed with a locally advanced or metastatic non-small cell lung cancer that has
             progressed despite standard therapy.

          -  Must have evidence of ALK 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:

          -  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 III-IV) .

          -  Active peptic ulcer disease or gastritis

          -  Major surgery within 4 weeks prior to starting PLB1003

          -  Previous anti-cancer and investigational agents within 4 weeks before first dose of
             PLB1003..

          -  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:Number of Participants With Dose Limiting Toxicities (DLTs) .
Time Frame:18 months.
Safety Issue:
Description:The maximum tolerated dose (MTD) was defined as the highest dose for a given schedule that was expected to cause DLTs in no more than 33% of patients during the first cycle of treatment.

Secondary Outcome Measures

Measure:Area under the plasma concentration versus time curve (AUC) of PLB1003 and its metabolite.
Time Frame:Day 1-3 PK Run-in period and Day 1-21 Treatment period
Safety Issue:
Description:In the study of PK Run-in period, full Pharmacokinetics (PK) profiles of PLB1003 will be obtained following administration of a single oral dose of PLB1003 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics (PK) sampling will include a pre-dose and at the 0.5, 2, 3,4, 6, 9, 10, 12 and 24 hour time points on days 1, 22 of dosing in the first 21-Day cycle of Treatment period, and pre-dose on days 16, 17 and 18 of the first 21-Day cycle of Treatment period.
Measure:Maximum plasma concentration observed (Cmax) of PLB1003 and its metabolite.
Time Frame:Day 1-3 PK Run-in period and Day 1-21 Treatment period
Safety Issue:
Description:In the study of PK Run-in period, full Pharmacokinetics (PK) profiles of PLB1003 will be obtained following administration of a single oral dose of PLB-1003 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics (PK) sampling will include a pre-dose and at the 0.5, 2, 3,4, 6, 9, 10, 12 and 24 hour time points on days 1, 22 of dosing in the first 21-Day cycle of Treatment period, and pre-dose on days 16, 17 and 18 of the first 21-Day cycle of Treatment period.
Measure:Time to Cmax (Tmax) of PLB1003 and its metabolite.
Time Frame:Day 1-3 PK Run-in period and Day 1-21 Treatment period
Safety Issue:
Description:In the study of PK Run-in period, full Pharmacokinetics (PK) profiles of PLB1003 will be obtained following administration of a single oral dose of PLB-1003 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics (PK) sampling will include a pre-dose and at the 0.5, 2, 3,4, 6, 9, 10, 12 and 24 hour time points on days 1, 22 of dosing in the first 21-Day cycle of Treatment period, and pre-dose on days 16, 17 and 18 of the first 21-Day cycle of Treatment period.
Measure:Preliminary antitumor activity of PLB1003.
Time Frame:30 months.
Safety Issue:
Description:Preliminary antitumor activity of PLB1003 assessed using RECIST1.1.

Details

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

Last Updated

April 23, 2017