Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin lymphoma.
Pretargeted radioimmunotherapy (PRIT) has the potential to increase the dose of radionuclide delivered to tumors while limiting radiation to normal tissues. The purpose of this phase 1 trial is to assess safety of this multistep approach using a novel tetrameric single-chain anti-CD20-streptavidin fusion protein (B9E9FP) as the targeting moiety in patients with B-cell non-Hodgkin lymphoma (NHL), and to characterize its pharmacokinetics and immunogenicity. All patients received B9E9FP (160 mg/m(2) or 320 mg/m(2)); either 48 or 72 hours later, a synthetic clearing agent (sCA) was administered (45 mg/m(2)) to remove circulating unbound B9E9FP. (90)Yttrium ((90)Y; 15 mCi/m(2))/(111)In (5 mCi)-DOTA-biotin was injected 24 hours later. There were 15 patients enrolled in the study. B9E9FP had a mean plasma half-life (T(1/2)) of 25 +/- 6 hours with a reduction in plasma level of more than 95% within 6 hours of sCA administration. (90)Y/(111)In-DOTA-biotin infusion resulted in rapid tumor localization and urinary excretion. The ratio of average tumor to whole-body radiation dose was 49:1. No significant hematologic toxicities were noted in 12 patients. There were 2 patients who had hematologic toxicity related to progressive disease. There were 2 complete remissions (90 and 325 days) and one partial response (297 days). B9E9FP performs well as the targeting component of PRIT with encouraging dosimetry, safety, and efficacy. A dose escalation trial of (90)Y-DOTA-biotin in this format is warranted.
University of Alabama at Birmingham Comprehensive Cancer Center, 35294-3300, USA. andres.forero@ccc.uab.edu
Andres
A
Forero
Paul L
PL
Weiden
Julie M
JM
Vose
Susan J
SJ
Knox
Albert F
AF
LoBuglio
Jordan
J
Hankins
Michael L
ML
Goris
Vincent J
VJ
Picozzi
Don B
DB
Axworthy
Hazel B
HB
Breitz
Robert B
RB
Sims
Richard G
RG
Ghalie
Sui
S
Shen
Ruby F
RF
Meredith
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018951:Antigens, CD20 / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D015902:Gamma Cameras; D006801:Humans; D016393:Lymphoma, B-Cell / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016499:Radioimmunotherapy / Q000009:adverse effects* / Q000379:methods; D011877:Radionuclide Imaging; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology / Q000493:pharmacokinetics; D014018:Tissue Distribution
D018951:Antigens, CD20; D011993:Recombinant Fusion Proteins