ESMO 2023 | DARWIN II: deciphering anti-tumor response & resistance to IO w/ intratumour heterogeneity in NSCLC

Crispin Hiley, PhD, UCL Cancer Institute, London, UK, shares an overview of the Phase II DARWIN II trial (NCT02314481), a multicenter, molecularly stratified trial designed to investigate how intratumor heterogeneity influences treatment response in patients with NSCLC. The DARWIN II trial enrolled 65 patients with metastatic NSCLC who had previously participated in the TRACERx Lung Cancer observational cohort study. They received atezolizumab or atezolizumab with chemotherapy. Multi-omic analysis of primary tumor and relapse biopsies revealed that a high clonal mutation burden was associated with a significantly improved response. Novel molecular features, including intratumor heterogeneity of the transcriptome and DNA methylation, were also linked to immunotherapy response. This study marks the first to prospectively show that clonal mutations and specific molecular features can predict immunotherapy outcomes in patients with NSCLC. This interview took place at the European Society for Medical Oncology (ESMO) 2023 Congress in Madrid, Spain.

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