Monitoring early clearance of circulating tumor DNA as an effective tool to predict clinical benefits of immune checkpoint inhibitors in lung cancer patients: The preliminary results from clinical trial NCT04203095.

Abstract

e15056 Background: Immuno-checkpoint inhibitors (ICI)is the stand-of-care of lung cancer treatment nowadays. But it’s still challenging to find an effective biomarker to predict clinical benefits from ICIs. Early data suggested that monitoring early clearance of circulating tumor DNA (ctDNA) as a tool to predict clinical benefits. Here we started a clinical trial (NCT04203095) to further validate it. Methods: 19 advanced non-small cell lung cancer patients who were planned to be treated with ICIs with or without chemotherapy were recruited consecutively since April 2019 ( NCT04203095 ). Clinical response was evaluated by RECIST 1.1 assessments at 12 weeks of treatments and afterward during 3-month interval visiting in the first year. Fresh plasma samples were collected -1 (before),+3 weeks and +12 weeks after the first dose. Plasma cell-free DNA(cfDNA) was send to low-coverage whole genome sequencing, followed by chromosomal instability (CIN) analyses by a customized workflow (UCAD). CIN scores were calculated by summarizing the copy number variations genome wide. Results: Early clearance of ctDNA was defined as Pearson correlations co-efficiency of copy number variations of cf DNA was below 0.65 between the baseline and 3 weeks after ICIs were administered. These 19 patients included 11 squamous cell carcinoma (SCC) and 8 adenocarcinomas. 8 of 11 respoonding patients showed early clearance of ctDNA, and 7 of 8 patients with SD or PD didn’t obtain early clearance of ctDNA. Meanwhile, clinical stage, histology, treatments (PD1 single or PD1+chemo combinations), sequence of treatment (first line, second line or multiple lines) did not predict clinical response, and baseline CIN score was not significantly correlated with clinical responses. In summary, only ctDNA early clearance was statistically significantly associated with clinical response (P = 0.020). Conclusions: Early clearance of plasma circulating tumor DNA at 3 weeks after treatments might be used a predictive biomarker of immune-checkpoint inhibition response. Clinical trial information: NCT04203095 .