13 October 2000, ESMO, Germany – Novel anticancer therapy CCI-779 targets abnormal cell growth, with a generally mild to moderate side-effect profile, according to new data 1 presented today at the European Society for Medical Oncology (ESMO) 2. Further findings revealing the role of CCI-779’s target, the recently discovered mTOR3 pathway, were also presented.
Preliminary results of CCI-779’s safety profile and anti-tumour activity were highlighted in a series of recent phase I clinical trials involving patients suffering multiple advanced cancers.
‘Our data suggest that CCI-779 inhibited tumour growth with only mild to moderate side effects over a broad range of doses’, says Dr Jean-Pierre Armand, Institut Gustave-Roussy, France. ‘These results, although preliminary, suggest CCI-779 shows exciting potential as a cancer treatment of the future’.
In one phase I trial, 21 patients were given weekly 30-minute intravenous infusions of CCI-779, on an increasing intermittent dosing schedule. In addition, tumour regression was observed in three patients with metastatic renal cell, neuro-endocrine and breast cancer, suggesting potential efficacy for CCI-779 in cancers where existing therapies have failed. Stabilisation of advanced disease was seen in ten patients, with two patients stabilising for 24 and 40 weeks.
On average, treatment lasted ten weeks, during which time no opportunistic infections were observed and no patient experienced prolonged immunosuppresion.
CCI-779 showed an encouraging mild to moderate toxicity profile. Its unique profile is primarily characterised by skin and mucosal side effects. These did not appear dose-related or cumulative, and where necessary, were treated with topical steroids.
‘In an ongoing study of 51 patients with solid tumours, we further examined the effects of escalating doses of CCI-779, administered five times daily every two weeks’, says Dr Hidalgo, University of Texas Health Science Center at San Antonio, USA. ‘Again, the toxicity profile and anti-tumour activity seen to date are encouraging’.4
Pre-clinical data
‘The breakdown of normal cell growth and division is a core feature of tumour development and a fundamental target for cancer therapy’, continues Dr Hidalgo. ‘CCI-779 is a novel drug, a rapamycin ester and the first to target the mTOR protein kinase. Although the exact function of mTOR requires further study, we do know that it is primarily involved in cell-cycle regulation’.
CCI-779’s unique mechanism of action targets key proteins that regulate inappropriate cell division and proliferation in the mTOR pathway. The anti-proliferative effects of CCI-779 indicate that this pathway, which may be applicable to many tumour types, has an essential role in cell division.
Data suggest that the normal function of the mTOR pathway is to coordinate cell growth and regulate progression through the cell cycle. CCI-779’s inhibition of the mTOR pathway may explain why it delays this phase of the cell cycle. In turn, further examination of this process may have implications for understanding why CCI-779 selectively arrests the development of certain cancer cells in tissue cultures.
In addition to CCI-779’s impact on the cell cycle, new data suggest CCI-779 may have selectivity in tumours where the PTEN tumour suppressor gene fails or mutates. These include endometrial (womb) and prostate cancers, which may form an especially sensitive subpopulation for CCI-779.
On the basis of promising safety and activity data from phase I trials supported by Wyeth Ayerst Pharmaceuticals, phase II studies are commencing in Europe and US in a range of tumour types.
For further information, please contact:
On-site at ESMO, 12-13 October:
Stephen Morgan, Ketchum, mobile + 44 7771 788067
Email: stephen.morgan@ketchumcomms.co.uk
Off-site, Europe:
Rebecca Hunt, Ketchum, tel: + 44 20 7465 7698
Email: rebecca.hunt@ketchumcomms.co.uk
Off-site, US:
Tami Holden, Ketchum, tel: + 1 202 835 9465
Email: tami.holden@ketchum.com
Notes for editors
1. mTOR – a novel target for cancer therapy, satellite symposium chaired by Dr Armand, ESMO 2000 – 13 October, Hall 8, Congress Centrum Hamburg, 12.45-14.45 CET.
2. ESMO – the 25 Congress of the European Society of Medical Oncology – runs 13-17 October 2000, Hamburg, Germany.
3. mTOR – the mammalian target of rapamycin
4. Hidalgo et al, A phase I and pharmacological study of CCI-779, a rapamycin ester cell cycle inhibitor, to be presented as an oral presentation at ESMO 2000 – 17 October, Hall 6, Congress Centrum Hamburg, 09.50am CET. Data embargoed until 09.50am, CET, 17-10-00.