A Phase 1 Study of 131I-CLR1404 in Patients with Relapsed or Refractory Advanced Solid Tumors: Dosimetry, Biodistribution, Pharmacokinetics, and Safety

Introduction: I-131-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK) and safety profiles of I-131-CLR1404. Methods: Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of I-131-CLR1404. Whole body planar nuclear medicine scans were performed at 15-35 minutes, 4-6, 18-24, 48, 72, 144 hours, and 14 days post injection. Optional single photon emission computed tomography imaging was performed on two patients 6 days post injection. Clinical laboratory parameters were evaluated in blood and urine. Plasma PK was evaluated on I-127-CLR1404 mass measurements. To evaluate renal clearance of I-131-CLR1404, urine was collected for 14 days post injection. Absorbed dose estimates for target organs were determined using the RADAR method with OLINDA/EXM software. Results: Single administrations of 370 MBq of I-131-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma 127 I-CLR1404 concentrations declined in a bi-exponential manner with a mean t(1/2) value of 822 hours. Mean Cmax and AUC(0-t) values were 72.2 ng/mL and 15753 ngNhr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow. Conclusions: Preliminary data suggest that I-131-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent.