First-in-human Phase I Study of a Selective c-Met Inhibit... | NCT02896231

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

NCT02896231

Sponsor

Beijing Pearl Biotechnology Limited Liability Company

Status

Completed

Last Update Posted

Nov 22, 2019Actual

Enrollment

37Actual

Phase

Phase 1

Conditions

Non-Small Cell Lung Cancer

Interventions

PLB1001

Countries

China

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Oct 2017

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Apr 2016

Primary Completion Date

Oct 2019Actual

Completion Date

Oct 2019Actual

First Submitted Date

Aug 16, 2016

First Submission Date that Met QC Criteria

Sep 6, 2016

First Posted Date

Sep 12, 2016Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Nov 20, 2019

Last Update Posted Date

Nov 22, 2019Actual

Oversight Module

Has Data Monitoring Committee (DMC)

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 1

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

37Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
PLB1001	Experimental	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

Interventions

Name	Type	Description	Arm Group Labels	Other Names
PLB1001	Drug	PLB1001 is a capsule in the form of 25 mg and 100mg, twice daily.	PLB1001

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of participants with dose-limiting toxicities		2 years

Secondary Outcomes

Measure	Description	Time Frame
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

Other Outcomes

Not provided

Eligibility Module

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

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms