Early trends of ctDNA levels in non-small cell lung cancer patients treated with immunotherapy (CLIP-IT): Pilot study.

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e15014 Background: Circulating tumor DNA (ctDNA) has been reported to be an independent prognostic indicator of outcome in lung cancer. The levels of ctDNA can correlate with changes in tumor burden in response to therapy. We assessed the utility of ctDNA levels as an early indicator of response to immunotherapy. Methods: Nineteen patients with advanced non-small cell lung cancer initiated on immune therapy were enrolled in this prospective trial. Blood collections were performed prior to treatment and with every cycle up to 4 cycles. Inivata’s InVisionSeq, an NGS-based 36 gene panel, analyzed the ctDNA. The trends of the ctDNA allele frequency was correlated with imaging responses post 4 cycles of therapy. Results: Patients included male 26%, median age 64 years, squamous 37%, adeno 63%, median cycles 4 with anti-PD1/PDL-1 therapy either alone or in combination with platinum-based chemotherapy. Four patients only had baseline ctDNA and were not evaluable. Clinical benefit was demonstrated in 9 (47.4%) patients (complete response (CR, n = 3), partial response (PR, n = 3) or stable disease (SD, n = 3)); 5 patients had progressive disease (PD) ;1 patient died of pneumonia after 2 cycles but showed decreasing ctDNA. In patients achieving clinical benefit, 8/9 had no detectable ctDNA following treatment, with the remaining patient (SD) having persistent ctDNA likely due to severe immune dermatitis. All 5 patients with PD had detectable ctDNA at progression. Six patients with detectable baseline ctDNA went on to demonstrate clinical benefit with > 50% decreases in ctDNA allele fractions by cycle 3. Absence of ctDNA at baseline and during therapy was indicative of clinical benefit (n = 3). In contrast, PD patients presented with increases in ctDNA allele fractions or detectable new ctDNA. Conclusions: Rapid decreases and clearance of ctDNA correlated with clinical benefit to immunotherapy. Increasing or newly detectable ctDNA was indicative of progressive disease or poor overall outcome. These results are promising and suggest the potential role of ctDNA as an early biomarker of response to immunotherapy.

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