Early Anti Cancer Clinical Drug Development
Our Drug Development Centre comprises a dedicated inpatient and outpatient facility for the treatment of cancer patients who have advanced cancer with little or no treatment options available. It is staffed by almost one hundred staff members including more than twelve physicians dedicated to drug development, with an ongoing drug development Research Fellowship program with or without translational research leading to a postgraduate degree (PhD or MD (Research)).
Our group works in close collaboration with other members of the Division of Cancer Therapeutics, overseen by Professor Paul Workman, specifically our GCP standard Pharmacokinetics Laboratory team run by Dr Florence Raynaud, and our Pharmacodynamics laboratory run by Dr Michelle Garrett and Dr Udai Banerji. Our Pharmacological Audit Trail work is conducted in close collaboration with these laboratories as well as Professor de Bono’s laboratory, which works on circulating tumour cells and other multi-purpose circulating biomarkers.
We also have a laboratory for sample processing and storage, which is run to Standard Operating Procedure by a dedicated laboratory manager on our Drug Development Unit inpatient facility. These are key to our conduct of the Pharmacological Audit Trail to ensure that we maximize the likelihood of patient benefit on early clinical trials and accelerate the successful clinical development of novel anticancer drugs as we have recently done with abiraterone acetate for advanced prostate cancer and the PARP inhibitor olaparib for cancers with a defect in BRCA function and DNA repair.
Overall, in conjunction with the Division of Cancer Therapeutics, our clinical drug development team is now established as one of the best Phase I Trial programmes in the world having successfully completed many Phase I clinical trials as our publication list below shows. We have conducted many first-in-human clinical trials of molecularly targeted agents (small molecules, antibodies, viruses and, antisense) aimed at growth factor or intracellular signalling (including EGFR, HER2, C-MET, PI3K, AKT, TOR kinase, BRAF, CRAF, MEK), angiogenesis (VEGFR1,2 and 3; CCL2), apoptosis (DR5, bcl-2), cancer epigenetics (DNA methyltransferase, HDAC) as well as DNA repair (PARP) and many other targets.
Our commitment is to optimize every individual patient’s chance of benefit and accelerate anticancer drug development through high quality clinical and translational research. In order to achieve this we are sequencing tumour nucleic acids of patients referred for trial participation for evidence of more than 200 DNA mutations that may associate with benefit from targeted treatments. Patients with identified tumour mutations are then stratified onto trials of agents targeting the mutation of interest eg PIK3CA, BRAF, RAS etc. This successfully led to clinical benefit for many patients with a BRCA carrier mutation when treated on our Phase I trial with the PARP inhibitor olaparib (Fong et al, New England Journal of Medicine, 2009; Fong et al, Journal of Clinical Oncology, 2010; Yap et al, The Cancer Journal, 2011).
We continue to run 20-30 Phase I trials at any time with the support of funding from an Experimental Cancer Medicine Centre (ECMC); Cancer Research UK; a Biomedical Research Centre grant from the Department of Health to the Royal Marsden as well as funding from The Institute of Cancer Research and The Royal Marsden Hospital.