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

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 PLB1003 in Patients With ALK-positive (ALK+) Advanced Non-small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03130881
• Other study ID #: HMO-PLB1003-20160828
• Status: Recruiting
• Phase: Phase 1
• Start date: November 8, 2016
• Est. completion date: December 30, 2021

Study information

• Verified date: April 2017
• Source: Beijing Pearl Biotechnology Limited Liability Company
• Contact: Peilong Zhang, Ph.D
• Phone: +86-10-64392756
• Email: zhangpeilong[@]pearlbio.cn
• 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 PLB1003.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 30, 2021
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• PLB1003
PLB1003 is a capsule and is administered orally.

Locations

Country	Name	City	State
China	Shanghai Chest Hospital	Shanghai	Shanghai

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	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.	18 months.
Secondary	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.	Day 1-3 PK Run-in period and Day 1-21 Treatment period
Secondary	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.	Day 1-3 PK Run-in period and Day 1-21 Treatment period
Secondary	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.	Day 1-3 PK Run-in period and Day 1-21 Treatment period
Secondary	Preliminary antitumor activity of PLB1003.	Preliminary antitumor activity of PLB1003 assessed using RECIST1.1.	30 months.