A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors
Cancer chemotherapy and pharmacology, 2013•Springer
Purpose The CC-chemokine ligand 2 (CCL2) is highly expressed in various malignancies
and promotes carcinogenesis. Blocking CCL2 has preclinical antitumor activity. A phase 1
trial of carlumab (CNTO 888), a human anti-CCL2 IgG1κ mAb, was conducted to evaluate
the safety, tolerability, pharmacokinetic–pharmacodynamic profile, and antitumor activity.
Methods Patients with advanced solid malignancy received escalating doses of carlumab
0.3, 1, 3, 10, or 15 mg/kg by 90-min intravenous infusion on days 1, 28, and every 2 weeks …
and promotes carcinogenesis. Blocking CCL2 has preclinical antitumor activity. A phase 1
trial of carlumab (CNTO 888), a human anti-CCL2 IgG1κ mAb, was conducted to evaluate
the safety, tolerability, pharmacokinetic–pharmacodynamic profile, and antitumor activity.
Methods Patients with advanced solid malignancy received escalating doses of carlumab
0.3, 1, 3, 10, or 15 mg/kg by 90-min intravenous infusion on days 1, 28, and every 2 weeks …
Purpose
The CC-chemokine ligand 2 (CCL2) is highly expressed in various malignancies and promotes carcinogenesis. Blocking CCL2 has preclinical antitumor activity. A phase 1 trial of carlumab (CNTO 888), a human anti-CCL2 IgG1κ mAb, was conducted to evaluate the safety, tolerability, pharmacokinetic–pharmacodynamic profile, and antitumor activity.
Methods
Patients with advanced solid malignancy received escalating doses of carlumab 0.3, 1, 3, 10, or 15 mg/kg by 90-min intravenous infusion on days 1, 28, and every 2 weeks thereafter (dose escalation) or 10 or 15 mg/kg every 2 weeks (dose-expansion). Pharmacodynamic assessments were also performed.
Results
Forty-four patients received 206 doses of carlumab. MTD was not established. Carlumab-related adverse events included grade 1–2 fatigue (9 %), nausea (7 %), headache (7 %), vomiting (5 %), and pruritus (5 %). The recommended phase II dose was 15 mg/kg every 2 weeks. Carlumab concentrations declined bi-exponentially with a terminal half-life of 6.6–9.6 days. Free CCL2 was transiently suppressed, while total CCL2 increased dose-dependently >1,000-fold post-treatment. A patient with ovarian cancer and a patient with prostate cancer achieved CA125 and PSA reductions of >50 % and RECIST SD for 10.5 and 5 months, respectively. Two other patients had RECIST SD for 7.2 and 15.7 months.
Conclusions
Carlumab was well tolerated with evidence of transient free CCL2 suppression and preliminary antitumor activity.
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