A Study of the Oral EGFR Inhibitor PLB1004 in Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a Phase I, multicenter, open-label, dose escalation and dose expansion study to assess the safety and pharmacokinetic profile of PLB1004, a mono-anilino-pyrimidine compound, given alone in NSCLC patients with EGFR exon 20 insertion mutations. Patients will be enrolled and dosed according to the most current protocol. This study is made of two Parts. Part 1 includes a dose escalation into 7 cohorts and patient allocation to these cohorts will be via slot allocation. Each cohort has a minimum of 3 and a maximum of 6 patients for a total of 21 - 42 patients. The patient population of the dose escalation phase will include patients with advanced NSCLC harboring EGFR classical mutations or Ex20ins mutations. Part 2 includes an expansion phase and the expansion phase will explore one or more dose levels of PLB1004 in NSCLC patients with EGFR Ex20ins mutations.

Official Title
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A Phase I Open-label, Multi-dose, Dose Escalation and Dose Expansion Study of the Oral EGFR Inhibitor PLB1004 in Non-Small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: PLB1004


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and willingness to sign a written informed consent document; Male or female adult patients 18 years of age or older; Patients should have recovered from toxicities related to prior anti-tumor therapy; Patients should have recovered from the effects of major surgery; Have a documented EGFR mutation by a local test in tissue or plasma; Inclusion criteria specific for Dose Escalation: Patients with a documented EGFR classical mutation or EGFR Ex20ins mutation, alone or in combination with other EGFR mutations; Inclusion criteria specific for Dose Expansion: Patients with a documented EGFR Ex20ins mutations (alone or in combination with other EGFR mutations); At least 12 weeks life expectancy; Must have at least one measurable lesion per RECIST v 1.1; Sexually active males and females of childbearing potential must agree to take effective contraceptive measures. Exclusion Criteria: Received radiotherapy within 14 days before enrollment; Have significant or uncontrolled systemic disease; Have significant or uncontrolled cardiovascular disease; Have had other diagnosed malignant diseases that required treatment within the past 3 years besides NSCLC; Currently have or had a history of interstitial lung disease, drug-induced interstitial lung disease, or radiation pneumonia that requires steroid therapy; Have known hypersensitivity to the similar drugs and excipients of PLB1004; Pregnant or lactating women; Have used other experimental drugs within 2 weeks prior to the first dose of PLB1004; Have any condition or illness that could affect the compliance with the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PLB1004<br>PLB1004 given as a mono-therapy in dose escalation and dose expansion phase. | Drug: PLB1004<br>* PLB1004 will be orally self-administered by the patient as a mono-therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile of PLB1004 per CTCAE v5.0 |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To define the DLTs and MTD |  | Up to 3 years | 
| Area Under the Curve (AUC) of PLB1004 |  | Approximately 28 days. | 
| Maximum plasma concentration (Cmax) of PLB1004 |  | Approximately 28 days. | 
| Time to maximum plasma concentration (Tmax) of PLB1004 |  | Approximately 28 days. | 
| Overall Response Rate (ORR) |  | Up to 3 years | 
| Progression-Free Survival (PFS) |  | Up to 3 years | 
| Overall Survival (OS) |  | Up to 3 years | 
| Disease Control Rate (DCR) |  | Up to 3 years | 
| Duration of Response (DOR) |  | Up to 3 years | 
| Change from baseline in corrected QT interval (QTc) using Fridericia formula (QTcF) |  | Up to 3 years |