Phase Ib study of CNTO 888 (anti-CCL 2) in combination with chemotherapies for treatment of patients with solid tumors.

3059 Background: CC-chemokine ligand 2 (CCL2) is expressed in various malignancies, implicated in angiogenesis, proliferation and metastasis. CNTO888 is a hIgG1κ mAb with selective high CCL2 binding affinity and showed preclinical antitumor activity. Methods: Primary objectives were safety and a recommended dose of CNTO 888 in combination with chemotherapy: Arm 1 - 15 mg/kg CNTO 888 + docetaxel 75 mg/m2 Q3W; Arm 2 - 15 mg/kg CNTO 888 + gemcitabine 1000 mg/m2 on D1 and 8 Q3W; Arm 3 - 15 mg/kg CNTO 888 + paclitaxel 175 mg/m2 and carboplatin AUC6 Q3W; Arm 4 - 10 mg/kg CNTO 888 Q2W + pegylated doxorubicin 50 mg/m2 Q4W. Two (Arms 1, 2, 3) or 4 (Arm 4) prior chemotherapies for advanced disease were allowed. Pharmacokinetic (PK) profile of CNTO 888 and chemotherapies, free and total CCL2, CTC/CEC count, and uNTX were evaluated. Adverse events (AE) and dose limiting toxicities (DLT) were evaluated after 6 subjects completed 1 cycle. Results: 53 subjects (22F/31M) were treated: Arm 1 n=15, Arm 2 n=12, Arm 3 n=12, ...