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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02896231
Recruitment Status : Completed
First Posted : September 12, 2016
Last Update Posted : November 22, 2019
Sponsor:
Information provided by (Responsible Party):
Beijing Pearl Biotechnology Limited Liability Company

Tracking Information
First Submitted Date  ICMJE August 16, 2016
First Posted Date  ICMJE September 12, 2016
Last Update Posted Date November 22, 2019
Study Start Date  ICMJE April 2016
Actual Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 6, 2016)
Percentage of participants with dose-limiting toxicities [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2016)
  • 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 ]
    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
  • Maximum plasma concentration observed (Cmax) of PLB1001 and its metabolite [ Time Frame: Day 1-2 Single Dose and Day 1-28 Steady State ]
    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
  • Time to Cmax (Tmax) of PLB1001 and its metabolite [ Time Frame: Day 1-2 Single Dose and Day 1-28 Steady State ]
    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
  • Preliminary antitumor activity of PLB1001 [ Time Frame: 2 years ]
    Preliminary antitumor activity of PLB1001 assessed using RECIST1.1
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE First-in-human Phase I Study of a Selective c-Met Inhibitor PLB1001
Official Title  ICMJE 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)
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE Drug: PLB1001
PLB1001 is a capsule in the form of 25 mg and 100mg, twice daily.
Other Name: Bozitinib
Study Arms  ICMJE Experimental: PLB1001
There 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.
Intervention: Drug: PLB1001
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 20, 2019)
37
Original Estimated Enrollment  ICMJE
 (submitted: September 6, 2016)
60
Actual Study Completion Date  ICMJE October 2019
Actual Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02896231
Other Study ID Numbers  ICMJE HMO-PLB1001-2013012-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Beijing Pearl Biotechnology Limited Liability Company
Study Sponsor  ICMJE Beijing Pearl Biotechnology Limited Liability Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Yilong Wu, MD Guangdong Provincial People's Hospital
PRS Account Beijing Pearl Biotechnology Limited Liability Company
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP