Multicenter phase 2 trial of ctDNA response after pembrolizumab in non-small cell lung cancer

BR.36 is a Canadian multicenter, randomized, circulating tumor DNA (ctDNA)-directed phase 2 trial of molecular response-adaptive immuno-chemotherapy for patients with advanced NSCLC. In the first stage of the trial, patients received pembrolizumab as standard of care. Primary objectives of stage 1 was to ascertain ctDNA response and determine optimal timing and concordance with RECIST response. The trial met its primary endpoint, with a sensitivity of ctDNA response for RECIST response of 82% and specificity of 75%. Median time to ctDNA response was 2,1 months, and patients with molecular response had longer progression-free and overall survival than patients without molecular response. These findings are incorporated in the ctDNA-driven interventional stage 2 of the trial, in which patients at risk of progression are randomized to treatment intensification or continuation of therapy.