Nsabp Fc-11: A Phase Ii Study Of Neratinib (N) Plus Trastuzumab (T) Or N Plus Cetuximab (C) In Patients (Pts) With "Quadruple Wild-Type (Wt)" (Kras/Nras/Braf/Pik3ca Wt) Metastatic Colorectal Cancer (Mcrc) Based On Her2 Status-Amplified (Amp), Non-Amplified (Non-Amp), Wt, Or Mutated (Mt).

TPS716Background: HER2 has been shown to be a validated therapeutic target for the treatment of mCRC. Preclinical and clinical evidence supports the use of HER2-targeted agents in each of these mCRC cohorts. In HERACLES, treatment–refractory, KRAS exon 2 (codons 12 and 13) WT, HER2 amp mCRC pts were treated with T and lapatinib (L). Objective response rate (CR or PR) was 8/27 and disease control rate (CR, PR, and SD u003e 16 wks) was 16/27. Duration of response ranged from 24-94+ wks. Anecdotal reports have shown activity of N in HER2 mts from several cancer types. In mCRC PDX models with qualifying HER2 mts, T plus N is more active than either drug alone. In quad WT, HER2 non-amp PDX models, C plus TKI resulted in major tumor regressions not seen with C monotherapy. In NSABP FC-7, a trial of C + N in cetuximab refractory pts, HER2 amp was observed in 2/23 primary tissue samples; after C exposure, HER2 amp was seen in 5/17 samples, presumably signal upregulation under selective pressure of C. HER2 amp was con...