Protocol Title
A Study to Evaluate ANS014004 in Combination with EGFR-TKI in Patients with EGFR Mutation-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer
The main purpose of this research study is to
Find a safe and tolerable dose of two investigational drugs, ANS014004 and PLB1004, when used together.
Learn how effective this drug combination is at treating a type of lung cancer called "EGFR mutation-positive non-small cell lung cancer (NSCLC)" that has spread to other parts of the body (locally advanced or metastatic).
This study is trying to answer the following questions:
Safety \& Dosing: What are the side effects of combining ANS014004 and PLB1004? What is the best dose to use that patients can tolerate well?
Effectiveness: Can this combination of drugs help shrink patients' tumors or stop them from growing?
Background Information
For patients with advanced lung cancer that has a specific gene change called an "EGFR mutation," targeted therapies known as EGFR-TKIs are a standard treatment. While these treatments often work well at first, most tumors eventually stop responding to the drug (this is called "acquired resistance"). The investigational drug ANS014004 is designed to block a protein called MET, which is one of the ways that tumors become resistant to EGFR-TKIs. The researchers believe that by combining ANS014004 with the EGFR-TKI PLB1004, they may be able to prevent or delay resistance, offering patients a more effective and longer-lasting treatment option.
How will the study be conducted?
This study is divided into two parts:
Part 1 (Dose Escalation and Optimization): A small number of participants will receive different dose levels of ANS014004 combined with a fixed dose of PLB1004. The goal is to find the safest and most tolerable dose combination.
Part 2 (Phase II Study): Once a recommended dose is identified, more participants will be enrolled to further evaluate how well the drug combination works against the cancer.
Throughout the study, participants' health will be closely monitored, and their tumors will be measured regularly using imaging scans (like CT scans) to see how they respond to the treatment.
Male or female participants ≥18years of age at the time of signing the informed consent form.
Patients with histologically or cytologically confirmed diagnosis of unresectable locally advanced (Stage IIIB and IIIC) or metastatic (Stage IV) NSCLC (according to the lung cancer staging criteria, refer to the eighth edition of the American Joint Committee on Cancer [AJCC] Lung Cancer Staging).
Have a documented EGFR positive mutation (EGFR classic mutations including ex19del and ex21 L858R, uncommon mutations and ex20 insertion mutations) in tumor tissue samples or pleural fluid or blood samples.
For Phase Ib dose escalation: have disease progression after the existing standard of care or intolerance to the existing standard of care or inappropriate or no effective standard of care is available (standard of care is defined as treatment recommended by the National Comprehensive Cancer Network [NCCN] guidelines [including but not limited to chemotherapy, radiotherapy, targeted therapy based on mutation status, immunotherapy, and surgery]). For participants who are considered intolerant to or ineligible for available standard therapy, or for whom effective standard therapy does not exist, the documentation of these reasons is required.
Have other known primary driver gene alterations. For example, NSCLC with a targetable alteration in ALK, RET, ROS1, BRAF, KRAS, etc. The investigators should discuss enrollment with the sponsor regarding co-mutations.
Prior treated with hepatocyte growth factor (HGF) targeted therapy or other MET-TKIs (including Type I and Type II), e.g., gulmonertinib, savolitinib, capmatinib, tepotinib, bozitinib, cabozantinib, glenitinib and almonertinib.
Participation in other therapeutic clinical trials within 28 days prior to the first dose of study treatment.
Nitrosourea or mitomycin-C within 6 weeks prior to the first dose of study treatment.
Beijing Pearl Biotechnology Limited Liability Company
Lead sponsor
Avistone Biotechnology Co., Ltd.
Collaborator