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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
PLB1003 is a capsule and is administered orally.
Shanghai Chest Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGNumber 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.
Time frame: 18 months.
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.
Time frame: Day 1-3 PK Run-in period and Day 1-21 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 frame: Day 1-3 PK Run-in period and Day 1-21 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.
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Time frame: Day 1-3 PK Run-in period and Day 1-21 Treatment period
Preliminary antitumor activity of PLB1003.
Preliminary antitumor activity of PLB1003 assessed using RECIST1.1.
Time frame: 30 months.