Anticancer agent – cixutumumab

A tyrosine kinase that is proving a popular target for potential anticancer therapies is insulin-like growth factor I receptor, or IGF-IR. It is overexpressed in a variety of different cancers, and seems to play a role in cancer cell proliferation. Both small molecule and antibody inhibitors of this receptor are being developed, including ImClone’s cixutumumab, a fully human immunoglobulin G1 monoclonal antibody with high affinity for IGF-IR.

In a first Phase I trial, 24 patients with advanced refractory or untreatable solid cancers were given escalating doses of 3, 6, 10 or 15mg/kg intravenously once a week for four weeks, followed by a two-week treatment free period.¹ It was fairly well tolerated; the most common adverse events included hyperglycaemia. There were no objective responses, but 11 patients – five from the 6mg/kg group – achieved stable disease, four of them for at least nine months.

Trials are ongoing in several different tumour types, both as monotherapy and in combination with other anticancer agents. In one Phase II study, it is being investigated in patients with thymoma and thymic carcinoma who have received at least one prior platinum containing regimen.² Subjects are given 20mg/kg of the antibody intravenously on the first day of a 21 day cycle. Of the first 13 patients dosed, after six months eight achieved stable disease, and the remainder disease progression. It was well tolerated, and adverse events included hyperuricaemia.

It is also being looked at as a single agent in prostate cancer. A total of 31 chemotherapy naïve patients with metastatic, asymptomatic or minimally symptomatic patients with castration-resistant prostate cancer were initially given 10mg/kg intravenous doses once every 21 days, and then in an ongoing follow up trial, the higher dose of 20mg/kg.³ Interim results showed a median time to progression of 4.8 months, and nine of the 28 evaluable patients remained on the study without progression for at least six months. Of these 28 patients, half achieved stable disease as a best response. Common adverse events included fatigue, nausea and hyperglycaemia, and the trial continues.

Numerous other trials are underway, with the drug being administered in combination with a variety of other anticancer agents, including temsirolimus, octreotide, sorafenib, capecitabine and lapatinib.

References

1. C. Higano et al. J. Clin. Oncol. 2007, 25 (suppl.), Abst. 3505
2. A. Rajan et al. J. Clin. Oncol. 2010, 28 (suppl.) Abst. e17525
3. C. Higano et al. J Clin Oncol. 2009, 27 (suppl.) Abst. 5142