Clinical trial NCT03130881: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Beijing Pearl Biotechnology Limited Liability Company
Sponsor class: INDUSTRY
First posted: 2017-04-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs) .
timeFrame: 18 months.
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC) of PLB1003 and its metabolite.
timeFrame: Day 1-3 PK Run-in period and Day 1-21 Treatment period
measure: Maximum plasma concentration observed (Cmax) of PLB1003 and its metabolite.
timeFrame: Day 1-3 PK Run-in period and Day 1-21 Treatment period
measure: Time to Cmax (Tmax) of PLB1003 and its metabolite.
timeFrame: Day 1-3 PK Run-in period and Day 1-21 Treatment period
measure: Preliminary antitumor activity of PLB1003.
timeFrame: 30 months.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Chest Hospital
name: Baohui Han, MD
role: PRINCIPAL_INVESTIGATOR
References: