Metastatic Melanoma

Melanoma is a form of skin cancer. There are over 150,000 cases diagnosed worldwide each year and incidence is increasing faster than in any other cancer. Patients diagnosed early are treatable with surgical resection, though in many the disease will recur. If melanoma continues to the later stages and becomes metastatic then the prognosis is poor, with a median survival of only 6–9 months. Chemotherapy is the most common treatment for patients with metastatic melanoma but the response rate is low. There is a high unmet need for more effective therapies for this disease.

IMCgp100

Immunocore has developed the drug IMCgp100 for the treatment of malignant melanoma. This human-specific soluble protein comprises a high- affinity T cell receptor (TCR) specific to a peptide sequence from the gp100 antigen, which is presented on melanoma tumour cells by HLA-A2, fused to an anti-CD3 single chain antibody fragment.

Immunocore has subjected IMCgp100 to efficacy and safety testing in the laboratory. Studies in vivo indicate that the drug demonstrates a significant anti-tumour activity at very low doses, ranging from 0.01 mg/Kg to 0.1 mg/Kg, and that this activity is antigen-specific.

Preliminary results suggest IMCgp100 kills cancer-initiating (stem) cells, the subset of tumour cells putatively responsible for initiating and maintaining the disease, as well as bulk tumour cells. This would make the drug useful in the adjunct therapy setting to prevent recurrence of melanoma after surgery, as well as for treatment of late stage disease.

Entering the clinic

IMCgp100 has received regulatory and ethics approval in the UK and USA and has entered clinical trials. 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. 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 trial will be conducted by the Abramson Family Cancer Research Institute at the University of Pennsylvania. Information about both trials is available at www.clinicaltrials.gov.

If you are interested in learning more about participation in Immunocore trials, please contact us at trials@immunocore.com