WCLC 2025 - Posters & ePosters-P3.18.72 Liquid Biopsy Guided Addition of Chemotherapy With TKI in Advanced EGFR Mutated NSCLC (LiquiACT)

Pdf Summary

The LiquiACT trial is an open-label, multicenter, phase 3 randomized controlled study evaluating a liquid biopsy-guided chemotherapy addition strategy for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Eligible patients are adults (≥18 years) with advanced NSCLC harboring sensitizing EGFR mutations and good performance status (ECOG 0–1), including those with treated asymptomatic brain metastases.<br /><br />Patients are randomized 1:1 into two arms. The control arm receives a combination of a tyrosine kinase inhibitor (TKI) of physician’s choice (osimertinib or gefitinib) plus platinum-based chemotherapy upfront. The experimental arm starts with TKI monotherapy for three weeks and adds chemotherapy only if high-risk features are detected: baseline circulating tumor DNA (ctDNA) positivity, failure to clear ctDNA by three weeks, or presence of TP53 co-mutations.<br /><br />Primary endpoint is 2-year overall survival (OS). Secondary outcomes include toxicity, quality of life (using EORTC QLQ-C30 and LC13 questionnaires), progression-free survival (PFS), and cost-effectiveness. The trial is designed as a non-inferiority study, assuming a 60% 2-year OS in the control arm, with a non-inferiority margin set at a hazard ratio of 1.3, powered at 90% with a 5% alpha level. The sample size target is 354 patients (177 per arm), accounting for 10% dropout.<br /><br />The rationale stems from prior evidence that upfront TKI plus chemotherapy improves PFS but causes increased toxicity. Risk factors identified via ctDNA and TP53 mutations may predict patients who truly benefit from added chemotherapy, allowing others to avoid unnecessary toxicity. The trial aims to establish whether a risk-adapted, ctDNA-guided chemotherapy addition is non-inferior to universal upfront combination therapy.<br /><br />The study commenced enrollment in March 2025 and is funded by the Indian Council of Medical Research. It is registered with the Clinical Trial Registry of India (CTRI/2025/01/079687). Investigators are from AIIMS New Delhi and Tata Memorial Centre Mumbai, India.

Asset Subtitle

Prabhat Malik

Meta Tag

Speaker Prabhat Malik

Topic Clinical Trials in Progress

Keywords

LiquiACT trial

liquid biopsy-guided chemotherapy

advanced EGFR-mutated NSCLC

tyrosine kinase inhibitor (TKI)

circulating tumor DNA (ctDNA)

TP53 co-mutations

overall survival (OS)

progression-free survival (PFS)

non-inferiority study

Indian Council of Medical Research