Phase I PK/PD study of RO5083945 (GA201), the first glycoengineered anti- EGFR monoclonal antibody (mAb) with optimized antibody dependent cellular cytotoxicity (ADCC).

2522 Background: RO5083945 is a glycoengineered anti EGFR IgG1 mAb exhibiting increased binding affinity for all FcγRIIIa variants expressed on immune effector cells. RO5083945 demonstrates significantly improved cell killing in ADCC-based assays and greater activity in in vivo models compared to cetuximab and panitumumab. Hence, RO5083945 has the potential to show clinical activity in patients with solid tumors, including KRAS mutant CRC. Methods: Patients (pts) with metastatic solid tumors were enrolled into part I of a phase I/II study of three regimens (qW, q2W and q3W), exploring up to 7 dose levels (50–1400 mg) to assess PK, MTD, AEs, PD and anti-tumor activity. Results: 75 pts were enrolled. No MTD was reached. Main AEs were infusion related reactions (77% of pts; mainly during the first infusion), rash (76%; 17% grade 3) and asymptomatic hypomagnesemia (24%; mainly grade 1/2). Among evaluable pts treated at 700–1400 mg, 3 pts (6%) had a partial response (2 confirmed, 1 recently reported) and 21 pt...