A Phase I, Open-label, Multicenter, Dose Escalation and Dose Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of PLB1004 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
Overview
- Phase
- Phase 1
- Intervention
- PLB1004
- Conditions
- Non-Small-Cell Lung Cancer
- Sponsor
- Avistone Biotechnology Co., Ltd.
- Enrollment
- 91
- Locations
- 1
- Primary Endpoint
- Incidence of Treatment-Emergent Adverse Events (TEAEs)
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a phase I, open-label, multicenter study to assess the safety, tolerability, pharmacokinetics and preliminary antitumor activity of PLB1004, and to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs) and recommended phase II dose (RP2D).
Detailed Description
The study includes a Dose-escalation Part and a Dose Expansion Part. The aim of the Dose-escalation Part is to estimate the MTD (if possible), identify the DLT (if possible) and the RP2D for PLB1004. The Dose Expansion Part is to further assess the clinical efficacy and safety of PLB1004.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Ability to understand and the willingness to sign a written informed consent document；
- •Aged at least 18 years old;
- •Histologically or cytologically confirmed advanced non-small cell lung cancer;
- •Patients with EGFR or HER2 mutations;
- •ECOG Performance Status of 0-2;
- •Life expectancy is not less than 12 weeks;
- •At least one measurable lesion as defined by RECIST1.1;
Exclusion Criteria
- •For the Dose Expansion Part: Patients who have received prior treatment with Poziotinib or TAK788 or other EGFR/HER2 exon20 insertion inhibitors should be excluded；
- •Any cytotoxic drugs or other anticancer drugs from a previous treatment regimen within 14 days prior to the first dose of PLB1004；
- •Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior (2 weeks for resection of brain metastases) to starting PLB1004 or who have not recovered from side effects of such procedure;
- •Thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting PLB
- •For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs), radiotherapy ≤ 2 weeks prior to starting PLB1004 or patients who have not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting PLB1004 is allowed;
- •Patients receiving treatment with medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with PLB1004 and for the duration of the study:
- •Strong inhibitors of CYP3A4
- •Strong inducers of CYP3A4
- •Inducers or inhibitors of P-gp
- •Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms;
Arms & Interventions
PLB1004
PLB1004 given alone as monotherapy.
Intervention: PLB1004
Outcomes
Primary Outcomes
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Time Frame: 2 years
A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
DLTs of Orally Administered PLB1004
Time Frame: 28 days
Toxicity will be evaluated according to the NCI CTCAE, Version 5.00. DLT will be defined as any of the events specified in the protocol that are considered by the investigator to be at least possibly related to therapy with study medications.
Maximum Tolerated Dose (MTD) of Orally Administered PLB1004
Time Frame: 28 days
The MTD is the highest dose level at which the participant tolerates treatment without dose-limiting toxicities.
Recommended Phase II Dose (RP2D) of Orally Administered PLB1004
Time Frame: 2 years
The RP2D is the maximum tolerated dose (MTD) or less. An RP2D less than the MTD may be chosen if aspects of tolerability or efficacy not encompassed by the MTD determination suggest utilizing a lower dose.
Secondary Outcomes
- Area Under the Curve (AUC) of PLB1004(Up to approximately 28 days; Pre-dose and multiple time points post-dose)
- Time to maximum plasma concentration (Tmax) of PLB1004(Up to approximately 28 days; Pre-dose and multiple time points post-dose)
- Overall Response Rate (ORR)(3 years)
- Progression-Free Survival (PFS)(3 years)
- Overall Survival (OS)(3 years)
- Maximum plasma concentration (Cmax) of PLB1004(Up to approximately 28 days; Pre-dose and multiple time points post-dose)
- Disease Control Rate (DCR)(3 years)
- Duration of Response (DOR)(3 years)