Phase I clinical study of the feasibility of pretargeted radioimmunotherapy (PT-RAIT) in patients with colorectal cancer (CRC): First results

358 Objectives PT-RAIT is being investigated in this phase I clinical trial to determine the optimal dose schedule using a humanized recombinant bispecific monoclonal antibody, TF2, targeting CEACAM5, and the hapten, histamine-succinyl-glycine (HSG), conjugated with 177Lu-labeled di-HSG-DOTA peptide IMP288 (DOTA-Gly-Lys(HSG)-Tyr-Lys(HSG)-NH2), in advanced CRC patients. Methods The intervals between the infusion of 75 mg TF2 and the i.v. injection of 100 µg 177Lu-IMP288 were 5 days (n=5)and 1 day (n=5). A pre-therapy cycle with 111In-labeled IMP288 was used to predict radiation dose of 177Lu and assure safety of high 177Lu doses (1st and 2nd cohorts of 3.7 and 7.4 GBq, respectively). Toxicity was determined by NCI-CTC v3.0.. Whole-body planar scintigraphy and SPECT were acquired up to 3 days post-injection (p.i.). Results In both cohorts TF2 administration was safe, with only mild grade-2 infusion reactions in 3 patients, controlled with antihistamines and corticosteroids, and with no other toxicities. TF2 cleared quickly from the blood, with Conclusions These first results confirm that CEACAM5-expressing CRC can be targeted with TF2 and 177Lu-IMP288 with minimal radiation exposure to normal organs, which allows for a multiple-dosing strategy. Research Support Dutch Cancer Society (KWF Kankerbestrijding) grant no. KUN 2008-403