Safety and tolerability of MIL-38/ Gallium67 (MILGa) in patients with advanced prostate, bladder and pancreatic cancer.

The investigational product “MILGa” is a chimeric MIL-38 monoclonal antibody targeting GPC-1, which has been chemically conjugated with the chelating agent DOTA and labeled with the radioisotope Gallium 67 (67Ga). MILGa is being developed for imaging metastases in prostate, pancreatic and bladder cancer patients. A total volume of 3-8ml (1mg of antibody at an activity of 250mBq) will be infused via slow IV push. The use of the chimeric MIL-38 monoclonal antibody conjugated to DOTA and labelled with 67Ga is safe and clinically useful for the detection of advanced prostate, bladder and pancreatic tumours. The addition of unlabelled chMIL-38-DOTA will aim to minimise binding of chMIL-38-DOTA-67Ga to non-tumour sites. The initial cohort of 3 patients will receive a 250 MBq imaging dose of chMIL-38-DOTA-67Ga. Cohort 1 (Patients 1, 2 and 3) *Patient 1: inpatient treatment with continuous monitoring for 48 to 72 h *Patient 2: Four weeks after patient 1, inpatient treatment with continuous monitoring for 24 to 48 h *Patient 3: Four weeks after patient 2, inpatient treatment with continuous monitoring for 24 to 48 h Cohort 2 (Patients 4, 5 and 6) Patients in this cohort will be infused with 3.5 mg of unlabelled chMIL-38-DOTA one hour prior to receiving 1 mg chMIL-38-DOTA labelled with 250 MBq 67Ga. Each patient in this cohort will be dosed 2 weeks apart and images using planar whole body scans and SPECT/CT. Cohort 3 (Patients 7, 8 and 9) Patients in this cohort will be infused with an incrementally higher dose within the range of 3.5 mg and 24 mg of unlabelled chMIL-38-DOTA one hour prior to receiving 1 mg chMIL-38-DOTA labelled with 250 MBq 67Ga. Each patient in this cohort will be dosed 2 weeks apart and images using planar whole body scans and SPECT/CT. Cohort 4 (Patients 10, 11 and 12) Patients in this cohort will be infused with an incrementally higher dose within the range of 3.5 mg and 24 mg of unlabelled chMIL-38-DOTA one hour prior to receiving 1 mg chMIL-38-DOTA labelled with 250 MBq 67Ga. Each patient in this cohort will be dosed 2 weeks apart and images using planar whole body scans and SPECT/CT. At end of each cohort: Safety assessment by DSMC and preliminary assessment of chMIL-38-DOTA-67Ga scan utility will be determined. Furthermore, the effect of the dose of un-labelled chMIL-38-DOTA used per cohort on tumour targeting will be reviewed at the end of each cohort to determine the unlabelled antibody dose for the subsequent cohort. Targeting of MILGa to patient’s metastases will be assessed by planar gamma imaging and SPECT/CT and compared to known metastases identified by standard of care imaging. Standard of care scans will be taken on the day of screening (visit 1) up to 14 days prior to MILGa infusion. Planar whole body and SPECT/CT imaging studies are planned as follows: *Transmission whole body scan with Cobalt-57 phantom prior to infusion with patient and without patient *Planar whole body imaging and, if required, SPECT/CT at T 30mins post infusion *Planar whole body imaging and, if required, SPECT/CT at T6h post infusion *Planar whole body imaging and SPECT/CT at T24h *Planar whole body imaging and, if required, SPECT/CT at T48h *Planar whole body imaging and, if required, SPECT/CT at T72h (Day 3) *Planar whole body imaging and SPECT/CT at T144h (Day6) *Planar whole body imaging at 2 weeks post infusion (if required) Any potential metastatic lesion identified on MILGa scanning but not visible on routine scans may be followed by standard radiology and, if possible, be biopsied later. Scan parameters: *Whole Body scan step-and-shoot, tri window of 300keV, 184keV and 93 with a window of +/- of 13%, 10%, 10%; Medium Energy Collimators; 180 second per step/bed-length. Whole body acquisition at 6hours, 24hours, 48hours, 72hours with the potential for further scans if required. *SPECT/CT: tri window of 300keV, 184keV and 93 with a window of +/- of 13%, 10%, 10% and a scatter correction window of 75 with a +/- window of 7%; Medium Energy Collimators; Step and Shoot 60/frames (or 6 degree intervals); 30second acquisition per step; Matrix 512x512; Attenuation Correction CT only; at 24hours and possibly 48hours. *Transmission whole body scans with Cobalt-57 phantom prior to patient infusion. One scan will be conducted with the patient, followed by a second scan without the patient. Each scan is approximately 25 minutes. The transmission whole body scan will be carried out for attenuation correction for isodosing of tissue. A nuclear medicine physicist will measure this.