Abstract 3721: DLL3 analysis of circulating tumor cells predict treatment outcome in phase 1 rova-T study in small cell lung cancer

Abstract

Abstract Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with early dissemination and poor prognosis that accounts for 15-20% of all lung cancer cases worldwide. Most cases are inoperable and biopsies to investigate SCLC biology are rarely obtainable. Circulating tumor cells (CTCs), which are prevalent in SCLC, present a readily accessible liquid biopsy. Here we present CTC data from aggressive, late stage SCLC patients who were enrolled on a Phase 1 trial studying Rova-T (anti-DLL3 antibody drug conjugate). CTCs were captured using a microfluidic platform (IsoFlux) that uses flow control and immunomagnetic capturing of epithelial cell surface marker (EpCAM)-positive cells. CTCs were isolated before dosing (baseline) of Rova-T and at successive time points post treatment. CTCs from each time point were distinguished and enumerated using DAPI, EpCAM and the cytoplasmic marker (pan-CK), in addition to the absence of CD45. Enriched CTCs were also collected for RT-PCR for expression analysis of genes confirmed to be absent in blood cells. The number of CTCs varied among the 58 baseline samples collected, ranging from 5-1000 CTCs per 7.5ml of blood. When the CTCs were assessed for DLL3 target expression, 37/58 baseline samples expressed DLL3 by RT-PCR. Interestingly, the expression of DLL3 on the baseline CTCs correlated with treatment outcome. When additional time points after treatment were enumerated for CTCs, patients that presented with DLL3 expression on CTC at baseline showed a significant decrease in CTCs after treatment. This suggests that Rova-T might kill DLL3-expressing CTCs. These data support continued investigation of DLL3 expression on CTC in SCLC patients with the goal of facilitating a liquid biopsy able to assess DLL3 status as a prospective companion diagnostic for Rova-T. Citation Format: Somdutta Roy, Kevin Martinez, Archana Dilip, Holger Karsunky, Scott Dylla. DLL3 analysis of circulating tumor cells predict treatment outcome in phase 1 rova-T study in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3721. doi:10.1158/1538-7445.AM2017-3721