Clinical trial NCT06046495: A Study of the Oral EGFR Inhibitor PLB1004 in Non-Small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Avistone Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-09-21
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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，uncommon mutations, classical mutations (Ex19del and L858R), and drug-resistant mutation (T790M). 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, or uncommon 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, classical mutations, or uncommon mutations.


Eligibility criteria: Inclusion Criteria:

1. Ability to understand and willingness to sign a written informed consent document;
2. Male or female adult patients 18 years of age or older;
3. Patients should have recovered from toxicities related to prior anti-tumor therapy;
4. Patients should have recovered from the effects of major surgery;
5. Have a documented EGFR mutation by a local test in tissue or plasma;
6. At least 12 weeks life expectancy;
7. Must have at least one measurable lesion per RECIST v 1.1;
8. Sexually active males and females of childbearing potential must agree to take effective contraceptive measures.

Exclusion Criteria:

1. Received radiotherapy within 14 days before enrollment;
2. Have significant or uncontrolled systemic disease;
3. Have significant or uncontrolled cardiovascular disease;
4. Have had other diagnosed malignant diseases that required treatment within the past 3 years besides NSCLC;
5. Currently have or had a history of interstitial lung disease, drug-induced interstitial lung disease, or radiation pneumonia that requires steroid therapy;
6. Have known hypersensitivity to the similar drugs and excipients of PLB1004;
7. Pregnant or lactating women;
8. Have used other experimental drugs within 2 weeks prior to the first dose of PLB1004;
9. Have any condition or illness that could affect the compliance with the protocol.

Primary outcomes:
measure: Safety profile of PLB1004 per CTCAE v5.0
timeFrame: Up to 2 years
Secondary outcomes:
measure: To define the DLTs and MTD
timeFrame: Up to 3 years
measure: Area Under the Curve (AUC) of PLB1004
timeFrame: Approximately 28 days.
measure: Maximum plasma concentration (Cmax) of PLB1004
timeFrame: Approximately 28 days.
measure: Time to maximum plasma concentration (Tmax) of PLB1004
timeFrame: Approximately 28 days.
measure: Overall Response Rate (ORR)
timeFrame: Up to 3 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to 3 years
measure: Overall Survival (OS)
timeFrame: Up to 3 years
measure: Disease Control Rate (DCR)
timeFrame: Up to 3 years
measure: Duration of Response (DOR)
timeFrame: Up to 3 years
measure: Change from baseline in corrected QT interval (QTc) using Fridericia formula (QTcF)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California-Davis
state: California
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: New York City
country: United States
facility: Research Site
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Seattle
country: United States
facility: Swedish Health Sciences
state: Washington
city: Seattle
country: United States
facility: Research Site
state: Washington
Study officials:
References: