457P - A first-in-human study evaluating the safety and pharmacology of MM-151, a novel oligoclonal anti-EGFR antibody combination in patients with refrac...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Drug Development
Translational Research
Presenter Wael Harb
Citation Annals of Oncology (2014) 25 (suppl_4): iv146-iv164. 10.1093/annonc/mdu331
Authors W. Harb1, C. Lieu2, M. Beeram3, L. Power4, C. Sloss4, J. Kearns4, R. Nering5, V. Moyo5, B. Wolf4, A.A. Adjei6
  • 1Oncology, Horizon BioAdvance, 47905 - Lafayette/US
  • 2Division Of Medical Oncology, University of Colorado, Denver, 80045 - Aurora/US
  • 3Oncology, The START Center for Cancer Care, 78229 - San Antonio/US
  • 4Clinical Research, Merrimack Pharmaceuticals, Inc., 02139 - Cambridge/US
  • 5Clinical Development, Merrimack Pharmaceuticals, Cambridge/US
  • 6/

Abstract

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.