A phase I, multicenter, open-label dosimetry study of I-131-CLR1404 in patients with relapsed or refractory advanced solid tumors who have failed standard therapy or for whom no standard therapy exists

• Published in: Journal of clinical oncology Vol. 30; no. 15_suppl; p. e13116
• Main Authors: Chao, Joseph, Mortimer, Joanne E., Cho, Steve Y., Marshall, John, Wong, Terence
• Format: Journal Article
• Language: English
• Published: 20.05.2012
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2012.30.15_suppl.e13116

Abstract only e13116 Background: I-131-CLR1404 is a small-molecule, iodophenyl-containing phospholipid ether analog that selectively delivers a cytotoxic beta-emitting radioisotope to cancer cells. In human tumor xenograft models, I-131-CLR1404 slowed malignant tumor growth and extended survival. Methods: A multi-center study evaluating total body and organ dosimetry, safety, and pharmacokinetics of 131-I-CLR1404 was conducted in 8 subjects with refractory solid tumors. We sought to determine the millicurie (mCi) dose of I-131-CLR1404 expected to deliver 35-40 centigray (cGy) to marrow, which will serve as the starting dose in a subsequent maximum tolerated dose (MTD) study. Subjects received a single dose of 10 mCi of I-131-CLR1404. Serial whole body planar scintigraphy images were obtained from 15 minutes to 6 days after I-131-CLR1404. Blood and urine samples were for biodistribution and pharmacokinetics. Results: Dosimetry calculations demonstrated consistency of organ and total body dosimetry in the 8 subjects. SPECT/CT images in a subset of patients indicated tumor-selective uptake of 131-I-CLR1404, showing a relative lack of uptake in adjacent normal tissue or bone marrow. No deaths or serious adverse events were reported during the study. A total of 7 subjects reported 19 AEs, 5 of which (all Grade 1) were considered by the investigator to be related to study medication. Based on the average red marrow dose of 0.56 mSv/MBq (2.09 rem/mCi), an administered activity of approximately 740 MBq (20 mCi will deliver 40 cGy (40 rem) to marrow, the starting dose in the Phase 1b (MTD) study. Conclusions: As a broad-spectrum, cancer-targeted molecular radiotherapeutic agent, I-131-CLR1404 may address at least two key limitations of current cancer therapies - lack of drug target expression and off-target toxicity. These results showan acceptable safety, dosimetry profile and selective uptake in malignant tumors. Further study of I-131-CLR1404 in cancer patients is warranted.