A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors: dosimetry, biodistribution, pharmacokinetics, and safety.
BACKGROUND
(131)I-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 (131)I-CLR1404.


METHODS
Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of (131)I-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 (127)I-CLR1404 mass measurements. To evaluate renal clearance of (131)I-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 (131)I-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 t½ value of 822 hours. Mean Cmax and AUC(0-t) values were 72.2 ng/mL and 15753 ng • hr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow.


CONCLUSIONS
Preliminary data suggest that (131)I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent.


BACKGROUND
ClinicalTrials.gov NCT00925275.
Cellectar Biosciences, Inc., Madison, WI, United States of America; Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States of America.
Joseph J
JJ
Grudzinski
Cellectar Biosciences, Inc., Madison, WI, United States of America; Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States of America.
Benjamin
B
Titz
Cellectar Biosciences, Inc., Madison, WI, United States of America.
Kevin
K
Kozak
Cellectar Biosciences, Inc., Madison, WI, United States of America.
William
W
Clarke
Cellectar Biosciences, Inc., Madison, WI, United States of America.
Ernest
E
Allen
Cellectar Biosciences, Inc., Madison, WI, United States of America.
LisaAnn
L
Trembath
Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States of America.
Michael
M
Stabin
Department of Medicine and Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington, DC, United States of America.
John
J
Marshall
Department of Radiology, Johns Hopkins Hospital, Baltimore, MD, United States of America.
Steve Y
SY
Cho
Department of Radiology, Duke University Medical Center, Durham, NC, United States of America.
Terence Z
TZ
Wong
Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, United States of America.
Joanne
J
Mortimer
Cellectar Biosciences, Inc., Madison, WI, United States of America; Department of Radiology, University of Wisconsin, Madison, WI, United States of America.
Jamey P
JP
Weichert
D000368:Aged; D005260:Female; D006801:Humans; D007462:Iodobenzenes / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009369:Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000532:radiotherapy*; D010742:Phospholipid Ethers / Q000494:pharmacology* / Q000627:therapeutic use*; D011874:Radiometry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D051598:Whole Body Imaging
C000599353:CLR1404; D007462:Iodobenzenes; D010742:Phospholipid Ethers