A phase I trial of antifibronecitin 131I-L19-small immunoprotein (L19-SIP) in solid tumors and lymphoproliferative disease

Abstract

2575 Background: L19-SIP is a human recombinant antibody-fragment consisting of the variable regions of the L19 mAb directed against the extra-domain B (ED-B) of fibronectin that is overexpressed in tumoral vasculature. We explored the targeting potential of 131I-L19-SIP for both tumor imaging and radioimmunotherapy (RIT). Methods: 131I-L19-SIP (4 mg; 74–193 MBq) was administered iv for dosimetry and pharmacokinetics (PK). Patients (pts) with high tumor uptake (lesion/red marrow absorbed dose ratio ≥10) received a single therapeutic dose of about 3,700 MBq (n=11) or 5,550 MBq (n=7) of 131I-L19-SIP. Dosimetry was based on dual-head gamma-camera planar imaging. Results: 37 pts (median age 59 yr [range 34–82], median ECOG PS 0 [range 0–1], median prior chemotherapies 2 [range 0–5]) with the following cancers were enrolled: colorectal (8), melanoma (7), thymoma (4), mesothelioma (4), prostate (2), pancreatic (2), lymphomas (2), other (8). Eighteen pts (48.6%) were eligible for RIT. Blood elimination profile in the first 13 pts: T1/2α 13 h, T1/2 β 39 h, with an extremely low interpatient variability. Dosimetry estimates as median absorbed doses (Gy): heart wall 2.8, kidneys 3.7, liver 3.0, lungs 1.98, testes 4.2, stomach 0.67, red marrow 0.85, tumor lesions 12.24. Imaging was excellent and in some cases revealed lesions undetected by MRI or CT. Main toxicities of RIT: short-lived grade 3/4 thrombocytopenia (4 pts) and uncomplicated grade 4 neutropenia (1 pt). One objective response was recorded according to RECIST criteria. A clinical benefit was seen in 4 additional pts: stabilization of ≥3 months in 1 thymoma pt, clinical evidence of long-term tumor shrinkage in 1 melanoma pt, stabilization of rapidly progressive skin lesions in 1 melanoma pt, and pain palliation in 1 breast cancer pt with brachial plexus neoplastic infiltration. Furthermore, a substantial decrease of [18F]FDG uptake was observed for several lesions in 3 out of 4 mesothelioma pts. Conclusions: Good tolerability and high tumor uptake combined with low red marrow absorbed dose justify testing the feasibility of further increase of the 131I-L19-SIP dose for RIT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer HealthCare Pharma, USA