A First-In-Human Study Evaluating the Safety and Pharmacology of Mm-151, a Novel Oligoclonal Anti-Egfr Antibody Combination in Patients with Refractory Solid Tumors

Aim: MM-151 is an oligoclonal combination of three IgG1, anti-EGFR antibodies designed to bind distinct non-overlapping EGFR epitopes and inhibit ligand-mediated signal amplification. MM-151's molecular composition enables antagonism of clinically relevant EGFR ligand mixtures, EGFR down-regulation and immune effector function (ADCC, CDC). A Phase 1 study was initiated to assess the safety, tolerability, PK, immunogenicity and preliminary clinical activity of MM-151. Methods: 69 patients were enrolled on 3 schedules (QW, Q2W, and Q3W) at escalating doses using standard 3 + 3 design. Response was assessed per RECIST criteria every 8 weeks. Patients continued on study until disease progression or unacceptable toxicity. Results: Results presented are based on preliminary data as of Apr. 25, 2014. 69 patients (median age 63 years; 33 male, 36 female) have been enrolled across 3 dosing schedules. 69 patients were evaluable for safety and 46 evaluable for efficacy. The most common tumor types were CRC (28 [41%]), NSCLC (9 [13%]), SCCHN (5 [7%]), and pancreatic (5 [7%]). An MTD has not been reached and dose escalation continues. Most adverse events were CTCAE grades 1 and 2. Infusion related reaction (IRR) was the most common AE (47 [68.1%]); however, this was managed with premedication and an optimized infusion schedule. The most common non-IRR AEs were comprised of EGFR-pathway toxicities, including rash (54 [78%]), hypomagnesemia (17 [25%]), mucositis (8 [12%]) and diarrhea (15 [22%]). Initial biomarker data in a subset of patients suggest that IRR relates to engagement of the innate immune system, shown in pre- and post - dose cytokine and peripheral blood flow cytometry data. Partial responses were observed in 2 CRC patients and a total of 8 (29% of mCRC) patients had SD for > 4 months (2 of the 8 had SD for 20.1 and 19.8 months). At doses > 9 mg/kg QW, trough total antibody levels at steady state were in expected therapeutic range. Conclusions: Results to date show that MM-151 has an acceptable safety profile and objective clinical activity in CRC. Updated safety, efficacy and preliminary biomarker data will be presented. Disclosure: C. Lieu: Consultant for Sanofi Aventis; L. Power, C. Sloss, J. Kearns, R. Nering, V. Moyo and B. Wolf: employee of Merrimack Pharmaceuticals, stock ownership. All other authors have declared no conflicts of interest.