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| |  Novel Anti-IGF-1 Receptor Drug, R1507, Shows Potential in Sarcoma Patients: Presented at AACR-NCI-EORTC By Crina Frincu-Mallos, PhD SAN FRANCISCO, CA -- October 25, 2007 -- The receptor for insulin-like growth factor 1 (IGF-1) is one of most potent natural activators of the AKT and MAPK signalling pathways, relevant in the development, growth, survival, and progression of cancer. One of the first clinical trials testing the potential of a novel anti-IGF-1 receptor therapy -- R1507 -- shows the drug to be safe, efficacious, and with few serious adverse effects in patients with sarcomas, researchers reported here at the 2007 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. A total of 34 patients with median age 55 years (range, 18-74 years; male: female ratio of 23: 11) were accrued in this phase 1 clinical trial of R1507, a human monoclonal antibody. The study is conducted at the M. D. Anderson Cancer Center and the University of Colorado Cancer Center. The drug, given weekly as a 1-hour infusion, was administered at three escalating dose levels of 1 mg/kg (n= 6), 3 mg/kg (n=6), and 9 mg/kg (n=22). The 9 mg/kg dose was expanded for additional assessment of drug efficacy and toxicity. The results, presented on October 23, show that 10 adult patients with advanced solid tumours experienced stable disease for a median duration of 18 weeks (range, 12-48 weeks). A total of four patients with Ewing's sarcoma were evaluable and had either a partial response (n=2) for 24 to 27+ weeks or stable disease (n=2) for 12 to 18+ weeks. Of the seven patients remaining on study, four have Ewing's sarcoma and the rest have leiomyosarcoma (n=1), osteosarcoma (n=1), or desmoplastic tumour (n=1). "For these patients to have control of their disease implies significant activity, but because the number of patients studied is so small, it is impossible to draw significant statistical conclusions," said one of the study's lead investigators, Stephen Leong, MD, Assistant Professor of Medical Oncology, University of Colorado Cancer Center, Denver, Colorado, United States. "This drug and others like it that attack the IGF pathway may provide a new class of drugs to treat a variety of cancers, including breast, prostate, colon, melanoma, myeloma, and a variety of sarcomas, which could greatly add to the way that we currently treat these patients," said Dr. Leong. Notably, 30 of the 34 patients (88%) had no drug-related toxicity of grade 2 or greater. In addition, there were no cases of hyperglycaemia, although the glucose tolerance test changed from negative to positive in two of 17 patients at week 7. There were two serious adverse effects reported during the trial: a cerebrovascular accident and hyperbilirubinaemia, both considered possibly related to the study drug at highest dose level. But it is not certain that the adverse events were caused by the drug, Dr. Leong said. "With a very small number of patients treated, the true and related side effects are still being evaluated," he said. Among the other drug-related adverse effects were fatigue, rash, nausea, diarrhoea, musculoskeletal pain, headache, dry eyes, and hypophosphataemia. The phase 1 study did not identify a dose-limiting toxicity or maximum tolerated dose, and, therefore, the recommended phase 2 dose is 9 mg/kg. The researchers explained that higher doses are not being tested because the trough concentration at the 9-mg/kg dose exceeds the target level needed for the IGF1R inhibition identified in preclinical studies. These results have led to the initiation of a phase 2 trial testing the agent in both paediatric patients and in adults with sarcoma. Funding for this study was provided by Roche Laboratories Inc.
[Presentation title: A Phase I Study of R1507, a Human Monoclonal Antibody IGF-1R (Insulin-like Growth Factor Receptor) Antagonist Given Weekly in Patients With Advanced Solid Tumors. Abstract A78]
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