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

Primary Purpose

Non-Small Cell Lung Cancer

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
PLB1001
Sponsored by
Beijing Pearl Biotechnology Limited Liability Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Guangdong General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PLB1001

Arm Description

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.

Outcomes

Primary Outcome Measures

Percentage of participants with dose-limiting toxicities

Secondary Outcome Measures

Area under the plasma concentration versus time curve (AUC) of PLB1001 and its metabolite
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
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
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
Preliminary antitumor activity of PLB1001 assessed using RECIST1.1

Full Information

First Posted
August 16, 2016
Last Updated
November 20, 2019
Sponsor
Beijing Pearl Biotechnology Limited Liability Company
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1. Study Identification

Unique Protocol Identification Number
NCT02896231
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
April 2016 (undefined)
Primary Completion Date
October 2019 (Actual)
Study Completion Date
October 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing Pearl Biotechnology Limited Liability Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PLB1001
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
PLB1001
Other Intervention Name(s)
Bozitinib
Intervention Description
PLB1001 is a capsule in the form of 25 mg and 100mg, twice daily.
Primary Outcome Measure Information:
Title
Percentage of participants with dose-limiting toxicities
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Area under the plasma concentration versus time curve (AUC) of PLB1001 and its metabolite
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
Time Frame
Day 1-2 Single Dose and Day 1-28 Steady State
Title
Maximum plasma concentration observed (Cmax) of PLB1001 and its metabolite
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
Time Frame
Day 1-2 Single Dose and Day 1-28 Steady State
Title
Time to Cmax (Tmax) of PLB1001 and its metabolite
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
Time Frame
Day 1-2 Single Dose and Day 1-28 Steady State
Title
Preliminary antitumor activity of PLB1001
Description
Preliminary antitumor activity of PLB1001 assessed using RECIST1.1
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yilong Wu, MD
Organizational Affiliation
Guangdong Provincial People's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Guangdong General Hospital
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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