(Oxford, UK, 5 October 2010) Researchers at Immunocore Limited today announced that IMCgp100, a targeted therapeutic for the treatment of advanced metastatic melanoma, has received regulatory and ethics approval and has opened enrolment for clinical trials in the UK and USA. IMCgp100 is the first clinical candidate originating from Immunocore’s innovative ImmTAC technology platform and a new treatment could benefit many thousands of patients diagnosed with skin cancer each year.
Melanoma is a form of skin cancer that accounts for less than five per cent of cases but causes the vast majority of skin cancer deaths. The American Cancer Society estimates that 68,130 new melanomas will be diagnosed in the US during 2010 and 8,700 deaths from this disease will occur. 10,672 cases were diagnosed in the UK in 2007 and there were 2,067 deaths in 2008. Incidence rates for melanoma have increased in the last thirty years and, unlike other common cancers, melanoma has a wide age distribution.
Patients who are diagnosed early are treatable with surgical resection, although in many the disease will recur within a few years. If melanoma continues to the late stages and becomes metastatic the prognosis is poor, with average survival times of six to nine months. Chemotherapy is the most common treatment, but the response rate is very low so there is a high level of unmet need for more effective therapies.
In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) Medicines Division has approved a Phase 1 dose finding study in patients with advanced malignant melanoma. The two-part study will establish a tolerable intravenous dose of IMCgp100 and then assess the effect of this dose on pharmacodynamic markers when given repeatedly to a larger group of patients.
Recruitment for the clinical trial has commenced at three leading hospitals in Oxford, Cambridge and Birmingham and the first patient has received treatment.
Professor Mark Middleton of the NIHR Biomedical Research Centre, Oxford said: “We need new treatment options for patients with metastatic melanoma that not only extend lives but also improve quality of life. This clinical trial will generate the first data on this promising novel reagent IMCgp100”.
Immunocore’s ImmTAC technology platform builds on expertise with high affinity T cell receptors and has the potential to target a range of cancer and chronic viral diseases that are not accessible to conventional monoclonal antibodies. IMCgp100 is the first product in the pipeline to enter a clinical trial and the company has recently secured significant new investment to take additional programmes into the clinic.
Dr Bent Jakobsen, founder and chief scientific officer of Immunocore, said: “We have worked for over ten years trying to overcome immune tolerance to cancer. Tumour cells often express only very low levels of their signature antigens and thereby hide from the immune system. We take human T cell receptors which recognise specific cancer antigens, in this case gp100 for melanoma, and enhance their binding affinity so that they can target the cancer cells. The engineered T cell receptor is bound to an antibody fragment that redirects T cells to destroy the bound tumour cell. I am very excited to see the first candidate advance into clinical trials”.
In the USA, the Food and Drug Administration (FDA) has approved a Phase 0 or Exploratory Trial. This study, in which the drug will be injected directly into melanoma tumours, is designed to complement the UK study by shedding light on how the drug works, and at what concentration.
“This is a novel approach to the challenge of mobilizing the immune system’s ability to recognise and disable cancer cells. In this study we will assess their effectiveness by analysing tumour samples from melanoma patients for evidence of local immune stimulation,” explains Professor Carl June, MD, director of translational research at the Abramson Family Cancer Research Institute (AFCRI) at Penn, which will conduct the US trial.
“The number of melanoma cases in the US is increasing and although early-stage melanoma can be treated surgically, we urgently need effective therapies to manage late stage metastatic disease,” notes Leslie Fecher MD, assistant professor of Medicine and principal investigator on the trial. “As a novel targeted immunotherapy, IMCgp100 may be a promising new approach to tackle this intractable disease.”
Further details of both trials are available at www.clinicaltrials.gov.
Note: The investigators in this study have no financial interest or other relationship with Immunocore Ltd, apart from their scientific collaboration in conducting laboratory experiments and planning human clinical trials.
PR Consultant, Immunocore Ltd, UK
T: +44 (0)1865 811199 E: firstname.lastname@example.org
About Metastatic melanoma
Melanoma is a form of skin cancer that accounts for less than 5% of cases but causes the vast majority of skin cancer deaths. The American Cancer Society estimates that about 68,130 new melanomas will be diagnosed in the United States during 2010 (about 38,870 in men; 29,260 in women) and 8,700 deaths from this disease will occur. 10, 672 cases were diagnosed in the UK in 2007 and there were 2,067 deaths in 2008. Incidence rates for melanoma have increased in the last thirty years and, unlike other common cancers, melanoma has a wide age distribution. In recent years, the increases have been most pronounced in young white women and older white men (www.cancer.org; www.cancerresearchuk.org).
Patients who are diagnosed early are treatable with surgical resection, although in many the disease will recur within a few years. If melanoma continues to the late stages and becomes metastatic the prognosis is poor, with average survival rates of only six to nine months. Chemotherapy is the most common treatment for patients with metastatic melanoma but the response rate is very low. There is a high level of unmet need for more effective therapies.
Immunocore Limited is developing innovative biological therapeutics to treat a range of cancers, chronic viral infections and diabetes. Immunocore is a privately owned biotechnology company located at Milton Park, near Oxford. The company traces its roots back to Avidex Limited which was founded in 1999 as a spin-out from the University of Oxford to develop technology invented by the founder and chief scientist, Dr Bent Jakobsen. Avidex was acquired in 2006 by the German company Medigene AG. In 2008, MediGene span out two independent companies based on the same core TCR enhancement technology platform; Immunocore to develop soluble protein therapeutics and Adaptimmune to develop cellular therapies. (www.immunocore.com).
IMCgp100 is a product derived from Immunocore’s ImmTAC™ technology platform.
ImmTACs couple the unique ability of affinity enhanced T Cell Receptors (TCRs) to target cancer and virally infected cells based on intracellular antigens that cannot be treated using traditional antibody based approaches, with a highly potent anti-CD3 mediated T cell redirection system.
Immunocore has developed processes that allow it to isolate human TCRs specific for a target of interest and to create soluble versions whose affinity has been enhanced several million fold. These engineered, disease -specific, TCRs are fused to an antibody fragment that binds a cell surface protein called CD3 which is found on the surface of the killer T cells of the immune system. ImmTACs target the diseased cells and redirect any T cell touching them to kill, even if that T cell would normally only recognise the common cold.
Unlike traditional immunotherapies such as cancer vaccines or immune-stimulating agents such as anti-CTLA4 antibodies, Immunocore’s ImmTACs have been specifically designed to overcome the antigen-down regulation that has limited the effectiveness of immunotherapies to date. Pre-clinical tests indicate that they can achieve potent T cell redirection against cancer cells that have lost almost all of their cell surface antigens through down-regulation.
IMCgp100 is an ImmTAC reagent specific for a peptide derived from the well validated target protein gp100, presented by HLA-A2; this target being present in approximately 50% of melanoma patients. IMCgp100 demonstrates potent activity against melanoma cells in vitro, including difficult to treat cancer stem cells.