Novel and more efficient anti-EGFR drugs capable to overcome acquired resistance to first generation of anti-EGFR inhibitors needs to be investigated.
MM151 is a mixture of three different monoclonal IgG1 antibodies directed toward three different, non-overlapping, epitopes of the EGFR. We performed an in vivo study by using human CRC cell lines (SW48, LIM 1215 and CACO2) which are sensitive to EGFR inhibitors, in order to evaluate the activity of MM-151 as compared to standard anti-EGFR mAbs, such as cetuximab, as single agent or in a sequential strategy of combination MM-151 with irinotecan (induction therapy) followed by MM-151 with a selective MEK1/2 inhibitor (MEKi) (maintenance therapy). Furthermore, the ability of MM-151 to overcome acquired resistance to cetuximab has been also evaluated in cetuximab-refractory CRC models.
MM151 shown stronger antitumor activity as compared to cetuximab. The maintenance treatment with MM-151 plus MEKi resulted the most effective therapeutic modality. In fact, this combination caused an almost complete suppression of tumor growth in SW48, LIM 1215 and CACO2 xenografts with a mean tumor volume of 13 mm3, 13 mm3 and 75 mm3, respectively at 30 week. Moreover, in this treatment group, mice with no evidence of tumor were more than double as compared to single agent treated mice. Its superior activity has also been demonstrated, in cetuximab-refractory CRC models.
These results provide experimental evidence that more efficient and complete EGFR blockade may determine better antitumor activity and could contribute to prevent and/or overcome acquired resistance to EGFR inhibitors.
Clinical trial identification
Legal entity responsible for the study
Università degli studi della Campania, “Luigi Vanvitelli”
Associazione Italiana per la Ricerca sul Cancro (AIRC)
All authors have declared no conflicts of interest.