ASKC202 Combined With Limertinib Versus Platinum-based Chemotherapy in Treatment of Locally Advanced or Metastatic NSCLC With MET Amplification/Overexpression After Failure of EGFR-TKI Therapy

Official title

A Randomized, Controlled, Open-Label, Multicenter, Phase 3 Study to Evaluate the Efficacy and Safety of ASKC202 in Combination With Limertinib Versus Platinum-based Chemotherapy in Participants With MET Amplification/Overexpression Locally Advanced or Metastatic NSCLC Who Have Failed After Prior EGFR-TKI Therapy.

Overview

This study is designed to compare the safety and efficacy of ASKC202 combined with Limertinib Versus platinum-based chemotherapy in locally advanced or metastatic NSCLC With MET Amplification/Overexpression after disease progression on EGFR tyrosine kinase inhibitor.

Detailed description

This is a randomized, controlled, open-label, multicenter, phase 3 clinical study to valuate the efficacy and safety of ASKC202 combined with Limertinib in locally advanced or metastatic NSCLC with MET amplification/overexpression after failure of EGFR inhibitor therapy. Participants will continue to receive treatment until disease progression, intolerable toxicity, withdrawal of informed consent, death, or any other reasons for treatment discontinuation, whichever occurs first.

Interventions

• Drug ASKC202+ Limertinib
  ASKC202 orally once per day (QD) combined with Limertinib orally BID for every cycle of 21 days until disease progression or other criteria for treatment discontinuation will be met.
• Drug Pemetrexed + Cisplatin /Carboplatin
  The standard chemotherapy treatment of cisplatin/carboplatin combined with pemetrexed on Day 1of 21 day cycles for 4\~6 cycles (every 3 weeks).

Primary outcome measures

• Progression-Free Survival (PFS) by BIRC [Time frame: 2 years]

Secondary outcome measures (6)

• Progression-free survival (PFS) by investigator [Time frame: 2 years]
• Overall Survival (OS) [Time frame: 3 years]
• Objective Response Rate (ORR) [Time frame: 2 years]
• Disease Control Rate (DCR) [Time frame: 2 years]
• Duration of Response (DoR) [Time frame: 2 years]
• Incidence and severity of treatment-emergent adverse events [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Willing and able to provide signed and dated informed consent;
• Patients at least 18 years of age;
• Locally advanced or metastatic non-small cell lung cancer (NSCLC);
• Objective disease progression following prior EGFR-TKI therapy;
• EGFR mutation with MET amplification/Overexpression by a central laboratory;
• Measurable lesions based on RECIST 1. 1;
• ECOG performance status 0 or 1;
• Expected survival >12 weeks;
• Adequate bone marrow reserve or organ function.

Exclusion criteria

• Prior or ongoing treatment with any c-Met target;
• Previously received systemic chemotherapy;
• Patients requiring continuous use of systemic immunosuppressants or systemic corticosteroids within 2 weeks prior to the first dose.
• Patients who underwent other major surgical procedures other than diagnosis or biopsy within 4 weeks prior to the first dose, or who were expected to undergo major surgeries during the study period;
• Prior to the first administration, there are unhealed toxic reactions of ≥ grade 2 (CTCAE 5.0 standard) associated with any previous treatment, any level of hair loss, and platinum drugs Except for grade 2 neuropathy caused;
• Patients with leptomeningeal metastasis, brainstem metastasis, or spinal cord compression;
• Presence of dysphagia or gastrointestinal disorders that may interfere with oral medication absorption;
• Previous history includes interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid therapy, or evidence of clinically active ILD；
• Have previously received hematopoietic stem cell transplants or solid organ transplants, or plan to receive hematopoietic stem cell transplants or solid organ transplants during the current period of study;
• There are serious or active infections that required intravenous antibiotics or hospitalization, such as HBV (HBsAg-positive and peripheral HBV-DNA titer test≥1×104 copies/mL or 2000 IU/mL), HCV, HIV, and syphilis;
• Serious or uncontrolled cardiovascular disease;
• Pregnant or lactating females;
• Other primary malignancies have been diagnosed within the last 5 years, and the following conditions can be enrolled: non-melanoma skin cancer, superficial bladder cancer, cervical carcinoma in situ that has undergone surgery and has been cured;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai East Hospital — Shanghai

Identifiers

NCT: NCT07109531 · ASKC202-301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗