Phase I trial of zalutumumab and irinotecan in metastatic colorectal cancer patients who have failed irinotecan- and cetuximab-based therapy

[Background:] Zalutumumab is a novel human IgG1 anti-EGFR mAb. We investigated the safety of zalutumumab and irinotecan in heavily pretreated mCRC patients. [Methods:] Metastatic CRC patients with documented progression (PD) during or within 6 months of stopping cetuximab and irinotecan based therapy were eligible. No prior treatment with anti-EGFR antibodies other than cetuximab was allowed. Patients received weekly doses of zalutumumab 8mg/kg and 16 mg/kg respectively in combination with irinotecan (180 mg/m2) every second week until PD or unacceptable toxicity. [Results:] The maximum tolerated dose was not reached and no patients experienced any dose limiting toxicity. At data cut-off (18-Dec-08) 4 patients had died (no cases of death were considered related to zalutumumab), 4 were off study due to PD and 1 was still ongoing (Table 1). In total, 6 patients experienced one or more grade 3/4 toxicities (diarrhea 2; neutropenia 2; leucopenia 1; abdominal pain 1; pulmonary embolism 1; alopecia 1). [Conclusions:] Zalutumumab can be safely administrated in doses up to 16mg/kg in combination with irinotecan in mCRC patients failing cetuximab and irinotecan based therapy. Zalutumumab and irinotecan resulted in durable stable disease warranting further investigation of this regimen.