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

Primary Purpose

Non-Small Cell Lung Cancer

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
PLB1003
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
  • 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

Sites / Locations

  • Shanghai Chest HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PLB1003

Arm Description

ALK-positive (ALK+) advanced NSCLC

Outcomes

Primary Outcome Measures

Number of Participants With Dose Limiting Toxicities (DLTs) .
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

Area under the plasma concentration versus time curve (AUC) of PLB1003 and its metabolite.
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.
Maximum plasma concentration observed (Cmax) of PLB1003 and its metabolite.
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.
Time to Cmax (Tmax) of PLB1003 and its metabolite.
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.
Preliminary antitumor activity of PLB1003.
Preliminary antitumor activity of PLB1003 assessed using RECIST1.1.

Full Information

First Posted
April 19, 2017
Last Updated
March 2, 2020
Sponsor
Beijing Pearl Biotechnology Limited Liability Company
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1. Study Identification

Unique Protocol Identification Number
NCT03130881
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Unknown status
Study Start Date
November 8, 2016 (Actual)
Primary Completion Date
December 30, 2020 (Anticipated)
Study Completion Date
December 30, 2021 (Anticipated)

3. Sponsor/Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
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 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.

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
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PLB1003
Arm Type
Experimental
Arm Description
ALK-positive (ALK+) advanced NSCLC
Intervention Type
Drug
Intervention Name(s)
PLB1003
Intervention Description
PLB1003 is a capsule and is administered orally.
Primary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicities (DLTs) .
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.
Time Frame
18 months.
Secondary Outcome Measure Information:
Title
Area under the plasma concentration versus time curve (AUC) of PLB1003 and its metabolite.
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.
Time Frame
Day 1-3 PK Run-in period and Day 1-21 Treatment period
Title
Maximum plasma concentration observed (Cmax) of PLB1003 and its metabolite.
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.
Time Frame
Day 1-3 PK Run-in period and Day 1-21 Treatment period
Title
Time to Cmax (Tmax) of PLB1003 and its metabolite.
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.
Time Frame
Day 1-3 PK Run-in period and Day 1-21 Treatment period
Title
Preliminary antitumor activity of PLB1003.
Description
Preliminary antitumor activity of PLB1003 assessed using RECIST1.1.
Time Frame
30 months.

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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peilong Zhang, Ph.D
Phone
+86-10-64392756
Email
zhangpeilong@pearlbio.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Baohui Han, MD
Organizational Affiliation
Shanghai Chest Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Chest Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200030
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Baohui Han, MD
Phone
+86-21-22200000
Email
xkyyhan@gmail.com
First Name & Middle Initial & Last Name & Degree
Tianqing Chu, MD
Phone
+86-21-22200000
Email
ctqxkyy@163.com
First Name & Middle Initial & Last Name & Degree
Baohui Han, MD
First Name & Middle Initial & Last Name & Degree
Tianqing Chu, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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