Anticancer agent – ganitumab
Insulin-like growth factor-I has started to garner attention as an oncology target; Amgen’s ganitumab is a fully human monoclonal IgG1 antibody against the IGF-1 receptor.
Insulin-like growth factor-I has started to garner attention as an oncology target. The trans-membrane tyrosine kinase IGF-1 receptor is found in normal tissue, and when activated by IGF-1 it is linked with tumour proliferation and the inhibition of apoptosis via the Ras/Raf/ERK/MAPK downstream pathway. It also interacts with other signalling pathways mediated by kinases such as VEGF and EGFR, all of which are established anticancer drug targets.
One potential treatment that acts at this receptor is Amgen’s ganitumab, a fully human monoclonal IgG1 antibody against the IGF-1 receptor.1 Numerous clinical trials have been carried out, and many more are under way, in various forms of solid tumours. In a Phase I study, 53 patients with advanced solid tumours or non-Hodgkin lymphoma were given escalating intravenous doses of the antibody every two weeks.2 One dose-limiting toxicity, grade III thrombocytopoenia, was seen, and aside from thrombocytopoenia the most common side-effects were fatigue, fever, rash, chills and anorexia.
The maximum planned dose of 20mg/kg was administered safely, and the maximum tolerated dose was thus not reached. One patient achieved a durable complete response, and there was one unconfirmed partial response, both in patients with Ewing sarcoma. The complete response lasted for more than two years on therapy. Two further patients with neuroendocrine tumours had a response – one unconfirmed partial, and the other minor.
Its potential was highlighted in a single case report of a patient with recurrent head and neck squamous cell carcinoma.3 The patient achieved a complete response to the combination of ganitumab and methotrexate after progressing on multiple cytotoxic agents and cetuximab.
A Phase IIb/III trial of the drug in comparison with rilotumumab in combination with panitumumab is under way; early biomarker data of the Phase II part was presented at this year’s ASCO meeting, and the trial is ongoing.4
1. P.J. Beltran et al. Mol. Cancer Ther. 2009, 8, 1095
2. A.W. Tolcher et al. J. Clinical. Oncol. 2009, 27, 5800
3. C.H. Chung et al. Head Neck online ahead of print, 2010 doi: 10.1002/hed.21478
4. C. Eng et al. J. Clinical. Oncol. 2011, 29 (Suppl.), Abst. 3500