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

Non-Small Cell Lung Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02896231
• Other study ID #: HMO-PLB1001-2013012-01
• Status: Completed
• Phase: Phase 1
• Start date: April 2016
• Est. completion date: October 2019

Study information

• Verified date: October 2017
• Source: Beijing Pearl Biotechnology Limited Liability Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: October 2019
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• PLB1001
PLB1001 is a capsule in the form of 25 mg and 100mg, twice daily.

Locations

Country	Name	City	State
China	Guangdong General Hospital	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Pearl Biotechnology Limited Liability Company

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with dose-limiting toxicities		2 years
Secondary	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	Day 1-2 Single Dose and Day 1-28 Steady State
Secondary	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	Day 1-2 Single Dose and Day 1-28 Steady State
Secondary	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	Day 1-2 Single Dose and Day 1-28 Steady State
Secondary	Preliminary antitumor activity of PLB1001	Preliminary antitumor activity of PLB1001 assessed using RECIST1.1	2 years