循环肿瘤 DNA (ctDNA) 在捕获免疫治疗的主要耐药性方面显示出了希望。 BR.36 是一项针对肺癌患者进行分子反应适应性免疫化疗的多中心、随机、ctDNA 导向的 2 期试验。在两个独立阶段的第一个阶段，50 名晚期非小细胞肺癌患者接受了派姆单抗作为标准治疗。第一阶段的主要目标是确定 ctDNA 反应并确定最佳时机以及与实体瘤 (RECIST) 反应放射学反应评估标准的一致性。次要终点包括评估 ctDNA 反应时间以及与无进展生存期和总生存期的相关性。帕博利珠单抗第三个周期的最大突变等位基因分数清除率标志着分子反应 (mR)。该试验达到了主要终点，ctDNA 响应对 RECIST 响应的敏感性为 82%（90% 置信区间 (CI)：52-97%），特异性为 75%（90% CI：56.5-88.5%）。 ctDNA 应答的中位时间为 2.1 个月（90% CI：1.5-2.6），mR 患者获得了更长的无进展生存期（5.03 个月 vs 2.6 个月）和总生存期（未达到 vs 7.23 个月）。这些发现被纳入 BR.36 试验的 ctDNA 驱动的介入分子反应适应性第二阶段，其中有进展风险的患者被随机分配接受强化治疗或继续治疗。 ClinicalTrials.gov ID：NCT04093167 .© 2023。作者。

Circulating tumor DNA (ctDNA) has shown promise in capturing primary resistance to immunotherapy. BR.36 is a multi-center, randomized, ctDNA-directed, phase 2 trial of molecular response-adaptive immuno-chemotherapy for patients with lung cancer. In the first of two independent stages, 50 patients with advanced non-small cell lung cancer received pembrolizumab as standard of care. The primary objectives of stage 1 were to ascertain ctDNA response and determine optimal timing and concordance with radiologic Response Evaluation Criteria in Solid Tumors (RECIST) response. Secondary endpoints included the evaluation of time to ctDNA response and correlation with progression-free and overall survival. Maximal mutant allele fraction clearance at the third cycle of pembrolizumab signified molecular response (mR). The trial met its primary endpoint, with a sensitivity of ctDNA response for RECIST response of 82% (90% confidence interval (CI): 52-97%) and a specificity of 75% (90% CI: 56.5-88.5%). Median time to ctDNA response was 2.1 months (90% CI: 1.5-2.6), and patients with mR attained longer progression-free survival (5.03 months versus 2.6 months) and overall survival (not reached versus 7.23 months). These findings are incorporated into the ctDNA-driven interventional molecular response-adaptive second stage of the BR.36 trial in which patients at risk of progression are randomized to treatment intensification or continuation of therapy. ClinicalTrials.gov ID: NCT04093167 .© 2023. The Author(s).