Clinical trial NCT02896231: First-in-human Phase I Study of a Selective c-Met Inhibitor PLB1001
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Beijing Pearl Biotechnology Limited Liability Company
Sponsor class: INDUSTRY
First posted: 2016-09-12
Enrollment: 37
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 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.

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

Primary outcomes:
measure: Percentage of participants with dose-limiting toxicities
timeFrame: 2 years
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC) of PLB1001 and its metabolite
timeFrame: Day 1-2 Single Dose and Day 1-28 Steady State
measure: Maximum plasma concentration observed (Cmax) of PLB1001 and its metabolite
timeFrame: Day 1-2 Single Dose and Day 1-28 Steady State
measure: Time to Cmax (Tmax) of PLB1001 and its metabolite
timeFrame: Day 1-2 Single Dose and Day 1-28 Steady State
measure: Preliminary antitumor activity of PLB1001
timeFrame: 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
Study officials:
affiliation: Guangdong Provincial People's Hospital
name: Yilong Wu, MD
role: PRINCIPAL_INVESTIGATOR
References: