Phase II Study of the Dual EGFR/HER3 Inhibitor Duligotuzumab (MEHD7945A) versus Cetuximab in Combination with FOLFIRI in Second-Line <i>RAS</i> Wild-Type Metastatic Colorectal Cancer.

Abstract

<b>Purpose:</b> Duligotuzumab is a dual-action antibody directed against EGFR and HER3.<b>Experimental Design:</b> Metastatic colorectal cancer (mCRC) patients with <i>KRAS</i> ex2 wild-type received duligotuzumab or cetuximab and FOLFIRI until progression or intolerable toxicity. Mandatory tumor samples underwent mutation and biomarker analysis. Efficacy analysis was conducted in patients with <i>RAS</i> exon 2/3 wild-type tumors.<b>Results:</b> Of 134 randomly assigned patients, 98 had <i>RAS</i> ex2/3 wild-type. Duligotuzumab provided no progression-free survival (PFS) or overall survival (OS) benefit compared with cetuximab, although there was a trend for a lower objective response rate (ORR) in the duligotuzumab arm. No relationship was seen between PFS or ORR and ERBB3, NRG1, or AREG expression. There were fewer skin rash events for duligotuzumab but more diarrhea. Although the incidence of grade ≥3 AEs was similar, the frequency of serious AEs was higher for duligotuzumab.<b>Conclusions:</b> Duligotuzumab plus FOLFIRI did not appear to improve the outcomes in patients with <i>RAS</i> exon 2/3 wild-type mCRC compared with cetuximab + FOLFIRI. <i>Clin Cancer Res; 24(10); 2276-84. ©2018 AACR</i>.