Biomarker Analysis From A Phase I Study Of Copanlisib With Expansion Cohorts In Solid Tumors With And Without Pik3ca Mutations And Nhl.

2548 Background: Copanlisib is a novel, selective, reversible, pan-Class I phosphatidylinositol-3-kinase (PI3K) inhibitor with potent activity against both the δ and α isoforms. Safety and tumor response data from the first-in-man phase I trial have been reported (Patnaik et al., 2012, ASH), with two patients with follicular lymphoma ongoing as of January 2015, with partial responses lasting 1380 and 909 days. A secondary objective of the study was to identify biomarkers associating with copanlisib response. Methods: After dose escalation, expansion cohorts were enrolled and treated at the maximum tolerated dose (0.8 mg/kg, iv, on days 1, 8 and 15 of a 28-day cycle), including solid tumors (n = 25) with and without PIK3CA mutations, and non-Hodgkin lymphoma (NHL; n = 9). PIK3CA, BRAF, and KRAS mutations were tested using digital PCR on archival tumor samples and circulating tumor (ct) DNA from plasma (BEAMing). Next generation sequencing (NGS) of tumor genes and IHC for PTEN were performed on archival tum...