Detection Of Endoglin-Expressing Ctcs In Patients Enrolled In An Adaptive Enrichment Phase 3 Trial Of Trc105 And Pazopanib Versus Pazopanib Alone In Patients With Advanced Angiosarcoma (Tappas).

e23570 Background: Endoglin (CD105) is an essential angiogenic receptor expressed on Angiosarcoma (AS) tumor cells and vessels that is upregulated following hypoxia and promotes resistance to VEGF inhibition. TRC105, an endoglin antibody, combined with pazopanib (P) achieved durable complete responses in AS patients, with encouraging median PFS of 7.8 months in chemotherapy-refractory and P-naïve patients enrolled in a Phase 1/2 trial. Here we report the capture of endoglin expressing circulating tumor cells (CTCs) using ApoStream dielectrophoresis field flow assist from the whole blood of AS patients enrolled in the ongoing Phase 3 TAPPAS trial. Methods: AS CTCs were enriched by ApoStream from samples drawn prior to treatment, with either TRC105/P or single agent P, at C1D1 and 6 weeks following initiation of study treatment at C3D1. CTCs that expressed CD105 and DAPI (nucleus) by immunofluorescence that used a non-competing endoglin antibody were quantified. CD105+/DAPI+ CTCs were further characterized as atypical cells using Diff-Kwik staining. Results: Forty (40) blood samples (25 at C1D1, 15 at C3D1) from 28 patients were analyzed. Paired pre- and post-treatment samples were available for 13 patients. Endoglin+ CTCs were detected in 100% (40/40) of samples (median = 1.5/mL; range 0.13 - 1,172/ml). Endoglin+ CTCs decreased between C1D1 and C3D1 in 13 patients with paired samples treated with TRC105/P or single agent P (C1D1 mean = 184.3/ml; median = 1.5/ml; range 0.13 - 1172/ml); C3D1 mean = 6.39/ml; median = 0.88/ml; range 0.44 - 26/ml). Diff-Kwik staining confirmed the enriched CTCs had atypical morphology containing hemosiderin deposits and large irregularly shaped nuclei in all cases. Conclusions: ApoStream technology isolated endoglin+ CTCs from the whole blood of AS patients. Decreases in endoglin+ CTCs were observed following treatment with TRC105/P and/or single agent P. Clinical trial information: NCT02979899.