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

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ClinicalTrials.gov Identifier: NCT02896231
Recruitment Status : Recruiting
First Posted : September 12, 2016
Last Update Posted : October 12, 2017
Sponsor:
Information provided by (Responsible Party):
Beijing Pearl Biotechnology Limited Liability Company

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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: PLB1001 Phase 1

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Study Start Date : April 2016
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: PLB1001
PLB1001 is a capsule in the form of 25 mg and 100mg, twice daily.
Other Name: Bozitinib




Primary Outcome Measures :
  1. Percentage of participants with dose-limiting toxicities [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. Preliminary antitumor activity of PLB1001 [ Time Frame: 2 years ]
    Preliminary antitumor activity of PLB1001 assessed using RECIST1.1



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02896231


Contacts
Contact: Weizhe Xue, Ph.D +86-10-64392756 xueweizhe@pearlbio.cn

Locations
China, Guangdong
Guangdong General Hospital Recruiting
Guangzhou, Guangdong, China, 510080
Contact: Jinji Yang, MD    +86-20-83827812 ext 50810    yangjinji2003@163.com   
Principal Investigator: Yilong Wu, MD         
Sub-Investigator: Jinji Yang, MD         
Sponsors and Collaborators
Beijing Pearl Biotechnology Limited Liability Company
Investigators
Principal Investigator: Yilong Wu, MD Guangdong General Hospital

Responsible Party: Beijing Pearl Biotechnology Limited Liability Company
ClinicalTrials.gov Identifier: NCT02896231     History of Changes
Other Study ID Numbers: HMO-PLB1001-2013012-01
First Posted: September 12, 2016    Key Record Dates
Last Update Posted: October 12, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms