Results of a randomized phase II trial of an anti-notch 2/3, tarextumab (OMP-59R5, TRXT, anti-Notch2/3), in combination with nab-paclitaxel and gemcitabine (Nab-P+Gem) in patients (pts) with untreated metastatic pancreatic cancer (mPC).
O'Reilly, EM; Sahai, V; Bendell, JC; Bullock, AJ; LoConte, NK; Hatoum, H; Ritch, PS; Hool, H; Leach, JW; Sanchez, J; Sohal, D; Strickler, JH ...
Published in: Journal of Clinical Oncology
279 Background: Tarextumab (TRXT), fully human IgG2 antibody inhibits signaling of Notch2/ 3 receptors. Tumor regression seen in Notch3 (N3) expressing pt-derived pancreatic cancer xenografts when TRXT combined with Nab-P+Gem. Phase 2, randomized, placebo-controlled trial conducted to evaluate efficacy, safety of combination in mPC. Methods: Pts randomized 1:1 to TRXT or placebo (PL). TRXT given IV at 15 mg/kg q 2wks (D 1, 15), nab-P 125 mg/m GEM 1000mg/m on D1, 8, 15 q 28 days. Tissue for N3 gene expression determination was required. Primary endpoints: overall survival (OS) in all and in 3 subgroups determined by Notch 3 gene expression. Secondary: safety, progression-free survival (PFS) and overall response rate (ORR). Results: N = 177 pts randomized. Performance status (0 or 1), CA19-9 stratum (0 – ULN, > ULN – 59ULN, ≥ 59ULN) balanced. Clinical trial information: NCT01647828. . Conclusions: Addition of TRXT to Nab-P+Gem did not improve OS in 1st line mPC. A potential detrimental effect on PFS and ORR was seen in subjects with N3 < 25%ile.[Table: see text]
