Abstract CT211: IMMU-130, an SN-38 antibody-drug conjugate (ADC) targeting CEACAM5, is therapeutically active in metastatic colorectal cancer (mCRC): Initial clinical results of two Phase I studies

摘要: IMMU-130, an ADC of the active metabolite CPT-11, SN-38, conjugated by a pH-sensitive linker (7.6 average drug-antibody ratio) to humanized anti-CEACAM5 antibody (labetuzumab), is completing two Phase I trials. In both, eligible patients with advanced mCRC were required have failed/relapsed standard treatments, one being topoisomerase-I inhibiting drug, CPT-11 (irinotecan), and elevated plasma CEA (>5 ng/mL). IMMU-130 was administered every 14 days (EOW) at doses starting from 2.0 mg/kg in first protocol (IMMU-130-01). Febrile neutropenia occurred 2 3 24 mg/kg; otherwise ≤16 mg/kg, (≥ Grade 2) observed 7 patients, also experiencing thrombocytopenia. One patient [of 8 who received > 4 (2 cycles)] showed 40.6% decrease liver (starting cm) lung target lesions (PR RECIST) for 4.7 months, no major toxicity, tolerating total 18 16 mg/kg. The study continuing 12 EOW. Since SN-38 most effective S-phase cells, more protracted exposure could improve efficacy. Thus, second trial (IMMU-130-02), dosing intensified twice-weekly, 6 mg/kg/dose weeks (4 doses) 1 week off, as treatment cycle, 3+3 design. Neutropenia manageable diarrhea side effects, until dose reduction 4.0 early results indicating multiple cycles are well-tolerated. Currently, tumor shrinkage PR (-46%) RECIST, among completed >4 (1 cycle). both trials, blood titers correlated response, high levels did not interfere therapy. There been anti-antibody or anti-SN-38 reactions, based on ELISA tests. each study, cleared 50% within h, which much longer than typical parental molecule, CPT-11. These indicate that this novel ADC, given different regimens averaging ∼16-24 mg/kg/cycle, shows therapeutic activity patients. CEACAM5 has expression breast cancers, well other epithelial tumors, it may be useful cancers well. A II evaluating twice-weekly new regimen, once-weekly x 21 days, ongoing mCRC. Citation Format: Neil H. Segal, Efrat Dotan, Jordan D. Berlin, Alexander N. Starodub, Michael J. Guarino, Leonard B. Saltz, Pius P. Maliakal, Serengulam V. Govindan, William A. Wegener, Robert M. Sharkey, David Goldenberg. antibody-drug conjugate (ADC) targeting CEACAM5, therapeutically metastatic colorectal cancer (mCRC): Initial clinical studies. [abstract]. In: Proceedings 105th Annual Meeting American Association Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Res 2014;74(19 Suppl):Abstract nr CT211. doi:10.1158/1538-7445.AM2014-CT211