Safety, pharmacology, and preliminary clinical activity of MM-151: An oligocolnal anti-EGFR theraputic in patients with cetuximab-resistant CRC and other refractory solid tumors.

647 Background: MM-151 is an oligoclonal anti-EGFR antibody combination designed to provide enhanced targeting of the EGFR network. This work describes the first in human experience of MM-151 alone and in combination with irinotecan. Methods: A standard 3+3 design was used to assess safety and tolerability of MM-151 monotherapy (QW, Q2W, Q3W) and MM-151 (QW) in combination with irinotecan 180mg/m2 (Q2W). A monotherapy expansion cohort has begun in cetuximab-resistant CRC. Results: Results presented are based on preliminary data as of September 2, 2014, for MM-151 monotherapy (n=65; QW/Q2W) and MM-151 in combination with irinotecan (n=10). The most common tumor types were CRC (29 [39%]), NSCLC (9 [12%]), HNSCC (8 [11%]). The monotherapy RP2D has been defined as 10.5 mg/kg QW and dosing continues at 18 mg/kg Q2W. Most adverse events were CTCAE grades 1 and 2. The most common AEs were toxicities related to the EGFR-pathway, including rash (70%), hypomagnesemia (24%), fatigue, dry skin, and diarrhea (21%). IRR was initially observed at high frequencies; however, standardized pre-medication and a modified infusion schedule significantly decreased this frequency. At doses >9 mg/kg QW, trough total antibody levels at steady state were in the expected therapeutic range. Of the CRC patients enrolled, 3 experienced Partial Responses (PRs) per RECIST criteria and a total of 8 (31%) pts had SD for >4 months. Initial biomarker data suggests particular clinical activity in triple-wildtype, EGFR-ligand positive CRC patients. Combination therapy with irinotecan continues with MM-151 at 9 mg/kg QW and 3 PRs have been observed (CRC, HNSCC, melanoma). Initial safety data is consistent with known toxicities of MM-151 and irinotecan. Preliminary results from the monotherapy expansion cohort (10.5 mg/kg QW) in CTX-refractory CRC will also be presented. Conclusions: These results demonstrate that MM-151 monotherapy has an acceptable tolerability profile and objective clinical activity alone and in combination with irinotecan. Results also support further clinical evaluation in triple-wildtype, EGFR-ligand positive CRC and other EGFR dependent cancers. Clinical trial information: NCT01520389.