Phase I study with antifibronectin I-131 L19-SIP: First dosimetric and therapeutic results

1681 Objectives: L19-SIP is a human Small Immuno-Protein (SIP) constructed using the variable regions of L19 against the ED-B domain of fibronectin, expressed only during angiogenesis and in tissue growth. Primary objective: dosimetric evaluation; Secondary objectives:toxicity, pharmakokinetics (PK) and therapeutic efficacy study. Methods: Patients (pts) with progressive disease with at least one lesion > 2.5 cm were studied.87-193 MBq of 131-I L19-SIP were administered for dosimetric and PK evaluation. Pts with lesion/red marrow absorbed dose ratio>10 were treated with 3.7 GBq. Pre-therapy dosimetric data collection included: blood samoples at 1,24,48,72,96h, urine up to 120h, daily whole body scans up to 96h, evaluation of organ and lesions volumes. Pts were followed for toxicity for at least 4 weeks after therapy; a CT scan was performed for tumor assessment. Results: 9 pts were studied (3 colorectal, 1 adenocortical, 1 renal cell, 1 breast carcinomas, 2 melanomas and 1 NSCLC plus urothelial carcinoma); 5 of them were treated. Slow component T1/2 in blood and in total body were 44.7 ±5.8h and 48.8 ±4.0h respectively. Median adsorbed doses were (Gy): liver 3.7(2.7-6.3);heart wall 2.0(1.6-2.4);spleen 5.9(3.8-9.4);kidneys 3.6(1.8-7.3);lungs 2.2(1.6-2.3);urinary bladder wall 1.9(1.4-2.1);red marrow 0.65(0.55-0.72);total body 0.6(0.4-0.8);tumor 8.5(6.8-27.5).Post-therapy drug related toxicities are limited to grade 4 thrombocytopenia in one severely malnourished patient. No other haematologhical toxicities occurred. No objective tumor response was observed. Clinical benefit was seen in 2 pts. Conclusions: The low red marrow dose, the absence of toxicity and the high tumor uptake have prompted the increase of therapeutic activity in order to characterize the toxicity and efficacy of the very promising I-131 L19-SIP. Research Support (if any): Study sponsored by Philogen SpA, Siena (Italy) and supported by Bayer Schering Pharma AG, Berlin (Germany).