Phase I trial of ¹³¹I-huA33 in patients with advanced colorectal carcinoma

Purpose: Humanized monoclonal antibody A33 (huA33) targets the A33 antigen which is expressed on 95% of colorectal cancers. A previous study has shown excellent tumor-targeting of iodine-131 labeled huA33 (¹³¹I-huA33). Therefore, we did a phase I dose escalation trial of ¹³¹I-huA33 radioimmunotherapy. Experimental Designs: Fifteen patients with pretreated metastatic colorectal carcinoma each received two i.v. doses of ¹³¹I-huA33. The first was an outpatient trace-labeled "scout" dose for biodistribution assessment, followed by a second "therapy" dose. Three patients were treated at 20, 30, and 40 mCi/m² dose levels, and six patients at 50 mCi/m² to define the maximum tolerated dose. Results: Hematologic toxicity was ¹³¹I dose-dependent, with one episode of grade 4 neutropenia and two episodes of grade 3 thrombocytopenia observed at 50 mCi/m². The maximum tolerated dose was determined to be 40 mCi/m². There were no acute infusion-related adverse events, and gastrointestinal toxicity was not observed despite uptake of ¹³¹I-huA33 in bowel. Seven patients developed pruritus or rash, which was not related to ¹³¹I dose. There was excellent tumor-targeting of ¹³¹I-huA33 shown in all patients. The serum T1/2β of ¹³¹I-huA33 was (mean ± SD) 135.2 ± 46.9 hours. The mean absorbed tumor dose was 6.49 ± 2.47 Gy/GBq. Four patients developed human anti-human antibodies. At restaging, 4 patients had stable disease, whereas 11 patients had progressive disease. Conclusion: Radioimmunotherapy using ^13lI-huA33 shows promise in targeting colorectal tumors, and is deliverable at a maximum tolerated dose of 40 mCi/m². Further studies of ¹³¹I-huA33 in combination with chemotherapy are planned.