Clinical And Biomarker Results From Phase I/Ii Study Of Pi3k Inhibitor Byl 719 (Alpelisib) Plus Nab-Paclitaxel In Her2-Negative Metastatic Breast Cancer

1018Background: Activation of Phosphatidylinositol-3-kinase (PI3K) pathway may confer resistance to taxanes and in preclinical models concomitant inhibition of the PI3K pathway enhances efficacy of taxanes. Alpelisib is a potent oral, class I inhibitor of PI3K alpha isoforms with antitumor activity in tumors that harbor PI3KCA mutations. Methods: Eligible patients had HER-2 negative MBC with any number of prior chemotherapy. Phase I was 3+3 dose-escalation design with three dose levels of alpelisib (250mg, 300mg, 350mg) PO daily (D1-28) and nab-Paclitaxel (nP) 100 mg/m2 D 1, 8, 15 every 28 days. Phase II was designed according to Simon’s Minimax design. Aims were to determine 1) Recommended Phase II Dose (RPTD), 2) Objective Response Rate (ORR), 3) Progression-free survival (PFS). PIK3CA activating mutations in tumor and circulating tumor DNA (ctDNA) were assessed using next-generation sequencing. Results: There were no DLTs in the three dose levels of phase I (n = 10). 33 patients were treated in phase I...