Safety and tolerability of Miltuximab® - a first in human study in patients with advanced solid cancers.

Objectives: Miltuximab^® is a chimeric antibody targeting Glypican-1 (GPC-1), a cell surface antigen which is overexpressed in solid cancers. Miltuximab^® has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. This first in human study used Miltuximab^® radiolabelled with Gallium-67 ([⁶⁷Ga]Ga-DOTA-Miltuximab^®). The primary study endpoint was to establish safety and tolerability of Miltuximab^®. Secondary endpoints were biodistribution, tumour targeting and pharmacokinetic analysis.

Methods: Four cohorts of three patients (9 with advanced prostate cancer, 2 with pancreatic and 1 with bladder cancer) were dosed with 1 mg, ~250 MBq of [⁶⁷Ga]Ga-DOTA-Miltuximab^®. Cohort 1 received [⁶⁷Ga]Ga-DOTA-Miltuximab^® alone, while cohorts 2-4 were pre-infused with increasing doses (3.5, 11.5 and 24 mg, respectively) of unlabelled Miltuximab^®-DOTA 1 hour prior to [⁶⁷Ga]Ga-DOTA-Miltuximab^®. Safety and tolerability were assessed by clinical and standard laboratory assessments. Patients underwent whole body gamma-camera scans and SPECT/CT scans up to 144 h post-infusion. Total organ radiation exposure was determined by dosimetry of whole-body gamma scans.

Results: The dosing regimen was well tolerated, with no drug-related adverse events observed. Liver and spleen uptake of [⁶⁷Ga]Ga-DOTA-Miltuximab^® was observed. Liver uptake was reduced by pre-infusion of unlabelled Miltuximab^®-DOTA. Dosimetry analysis showed a favorable exposure profile. [⁶⁷Ga]Ga-DOTA-Miltuximab^® targeting to tumour sites was observed in two prostate cancer patients who had failed enzalutamide treatment. Higher doses of unlabelled antibody achieved lower liver uptake and increased antibody serum half life.

Conclusions: This study is the first in human for Miltuximab^® a first in class antibody targeting GPC-1. The trial met its primary endpoint of safety, demonstrating its potential as a safe and tolerable monoclonal antibody. This safety data, together with targeting to tumour lesions and biodistribution information supports the further clinical development of Miltuximab^® as a theranostic agent in a planned Phase I human trial.