Development of an imaging-guided CEA-pretargeted radionuclide treatment of advanced colorectal cancer: first clinical results.
Br J Cancer
; 109(4): 934-42, 2013 Aug 20.
Article
in En
| MEDLINE
| ID: mdl-23860529
ABSTRACT
BACKGROUND:
Radiolabelled antibody targeting of cancer is limited by slow blood clearance. Pretargeting with a non-radiolabelled bispecific monoclonal antibody (bsMAb) followed by a rapidly clearing radiolabelled hapten peptide improves tumour localisation. The primary goals of this first pretargeting study in patients with the anti-CEACAM5 × anti-hapten (HSG) bsMAb, TF2, and the radiolabelled hapten-peptide, IMP288, were to assess optimal pretargeting conditions and safety in patients with metastatic colorectal cancer (CRC).METHODS:
Different dose schedules were studied in four cohorts of five patients (1) shortening the interval between the bsMAb and peptide administration (5 days vs 1 day), (2) escalating the TF2 dose (from 75 to 150 mg), and (3) reducing the peptide dose (from 100 to 25 µg). After confirmation of tumour targeting by (111)In-IMP288, patients were treated with a bsMAb/(177)Lu-IMP288 cycle.RESULTS:
Rapid and selective tumour targeting of the radiolabelled peptide was visualised within 1 h, with high tumour-to-tissue ratios (>20 at 24 h). Improved tumour targeting was achieved with a 1-day interval between the administration of the bsMAb and the peptide and with the 25-µg peptide dose. High (177)Lu-IMP288 doses (2.5-7.4 GBq) were well tolerated, with some manageable TF2 infusion reactions, and transient grades 3-4 thrombocytopaenia in 10% of the patients who received (177)Lu-IMP288.CONCLUSION:
This phase I study demonstrates for the first time that pretargeting with bsMAb TF2 and radiolabelled IMP288 in patients with CEA-expressing CRC is feasible and safe. With this pretargeting method, tumours are specifically and rapidly targeted.
Full text:
1
Database:
MEDLINE
Main subject:
Oligopeptides
/
Colorectal Neoplasms
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Carcinoembryonic Antigen
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Radioimmunotherapy
/
Antibodies, Bispecific
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Haptens
/
Heterocyclic Compounds, 1-Ring
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Br J Cancer
Year:
2013
Type:
Article
Affiliation country:
Netherlands