Betalutin publications highlight benefits of predosing regimen


Lilotomab predosing of NHL patients before Betalutin therapy lowers haematological toxicity with no reduction in the tumour absorbed radiation dose

Nordic Nanovector announces that two papers recently published in The Journal of Nuclear Medicine have shown that predosing with the anti-CD37 antibody lilotomab (previously referred to as HH1), prior to injection with Betalutin (177Lu-lilotomab) reduces haematological toxicity without adversely impacting the amount of radiation absorbed by the tumour.

Betalutin is a novel anti-CD37 antibody-radionuclide-conjugate (ARC) currently in Phase I/IIa. Two predosing regimens have been investigated, one with 40mg of unlabelled lilotomab antibody (Arm 1) and one without (Arm 2). Data from eight patients were included in both papers.

The first paper looked at the risk that predosing with lilotomab could block the CD37 antigen on tumour tissues adversely impacting the amount of radiation absorbed by the tumour.

The research shows that there was no difference in the tumour absorbed dose for patients in Arm 1 and Arm 2. The reduced distribution volume and clearance in Arm 1 might explain this finding as it implies that the concentration of Betalutin in the blood was higher for Arm 1 patients than for Arm 2 patients, therefore increasing concentration counteracts any eventual blocking of CD37 on tumour tissue.

The second paper looked at the radiation exposure of the red bone marrow (RM), which is often the primary organ at risk in radioimmunotherapy. Irradiation of the marrow may induce short- and long-term haematological toxicity.

Researchers found that the RM radiation doses were significantly higher in the patients who did not receive predosing. This difference indicates that predosing with lilotomab has a protective effect for RM, most likely thanks to the unlabelled antibody, which blocks the binding to CD37 in the RM.

Jostein Dahle, Nordic Nanovector CSO, commented: 'The results outlined in these two publications further support our hypothesis that predosing with lilotomab provides a protective effect on healthy tissues when used prior to Betalutin treatment and, importantly, that predosing does not adversely impact the radiation absorbed by the tumour.'

'These findings also support our development strategy for Betalutin, where we are looking at different predosing regimens to identify the optimal dose regimen of this novel antibody-radionuclide-conjugate to take into later stage clinical trials,' he added.

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The Lymrit 37-01 study is a Phase I/II open label, single injection ascending dose study investigating three dose levels of Betalutin and different predosing regimens in patients with relapsed NHL with the aim of identifying an optimal dose regimen to take into the Phase 2 PARADIGME study, which is expected to start in 2H 2017.