Page 1 of 27 Phase II study of the dual EGFR/HER3 inhibitor duligotuzumab (MEHD7945A) versus cetuximab in combination with FOLFIRI in second line RAS wild-type metastatic colorectal cancer

Purpose: Duligotuzumab is a dual-action antibody directed against EGFR and HER3. Experimental design: mCRC patients with KRAS 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 RAS exon 2/3 wild-type tumors. Results: Of 134 randomized patients, 98 were RAS ex2/3 wild-type. Duligotuzumab provided no PFS or OR benefit compared to cetuximab; though there was a trend for lower 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. Conclusions: Duligotuzumab plus FOLFIRI did not appear to improve the outcomes in patients with RAS exon 2/3 wild-type mCRC compared to cetuximab + FOLFIRI. Statement of translational relevance Duligotuzumab, a dual-action antibody to EGFR and HER3, shows preclinical efficacy in EGFRdependent CRC cell lines refractory to EGFR inhibition. We evaluated duligotuzumab compared to cetuximab in combination with FOLFIRI as second-line therapy in patients with RAS exon 2/3 wild-type metastatic CRC and found no advantage to duligotuzumab. on April 2, 2018. © 2018 American Association for Cancer Research. clincancerres.aacrjournals.org Downloaded from Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on March 5, 2018; DOI: 10.1158/1078-0432.CCR-17-0646