An Open-label, Multicenter Phase Ib/II Study to Evaluate the Safety, Efficacy and Pharmacokinetic Characteristics of ANS014004 in Combination With EGFR-TKI in Patients With EGFR Mutation-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Summary

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.

Eligibility

Age range

18+ years

Sex

All

Healthy volunteers

No

Interventions

• Drug
  ANS014004 + PLB1004

  1. Drug: ANS014004 Investigational Type II MET tyrosine kinase inhibitor (oral tablets). Dosing: Phase Ib escalation (30 mg, 45 mg, 60 mg, 75 mg QD); optimization uses selected doses; Phase II uses RP2D. Administered QD (≥1h before/2h after meals) in 21-day cycles. Targets MET exon 14 skipping, amplification, overexpression, and fusions. 2. Drug: PLB1004 Investigational irreversible EGFR tyrosine kinase inhibitor (oral capsules). Fixed dose: 80 mg QD. Administered QD (≥1h before/2h after meals) in 21-day cycles. Targets EGFR classical mutations (Ex19del, L858R), rare mutations, Ex20ins, and T790M.

• Drug
  ANS014004 + Osimertinib

  1. Drug: ANS014004 (Same description as above, as the drug is identical across arms). 2. Drug: Osimertinib Market-approved third-generation EGFR tyrosine kinase inhibitor (oral tablets). Dosing: Per reference label (QD, with/without meals). Administered in 21-day cycles. Targets EGFR classical mutations (Ex19del, L858R) and T790M. Used as an active comparator.

Location