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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: PLB1004

• Study Type: Interventional
• Enrollment (Estimated): 81
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Avistone Clinical Study Information Center Center; Phone Number: +86-10-84148921; Email: information.center@avistonebio.com

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817-1514
      • Recruiting
      • University of California-Davis
      • Contact: Study Director, MD
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Recruiting
      • Nebraska Cancer Specialists
      • Contact: Study Director, MD
  • New York
    • New York City, New York, United States, 100021
      • Recruiting
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
      • Contact: Study Director, MD
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • Research Site
    • Seattle, Washington, United States, 98122
      • Recruiting
      • Swedish Health Sciences
      • Contact: Study Director, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	Up to 3 years
Overall Response Rate (ORR)	Up to 3 years
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.
Progression-Free Survival (PFS)	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

Collaborators and Investigators

• Sponsor: Avistone Biotechnology Co., Ltd.
• Investigators: Study Director: Weizhe Xue, Ph.D, Avistone Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2024
• Primary Completion (Estimated): February 9, 2028
• Study Completion (Estimated): February 9, 2028

Study Registration Dates

• First Submitted: September 6, 2023
• First Submitted That Met QC Criteria: September 19, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: PLB1004-I-US01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No