Trial of IMCgp100, durvalumab and tremelimumab in melanoma starts

Immunocore has started a Phase Ib/II combination trial evaluating IMCgp100 in combination with durvalumab and tremelimumab for the treatment of metastatic cutaneous melanoma.

IMCgp100 is Immunocore’s lead ImmTAC (Immune Mobilising Monoclonal T-Cell Receptor Against Cancer). ImmTACs are a new class of drug with ultra-high affinity for intracellular cancer targets and are synthetic, soluble T cell receptors (TCRs) that recognise diseased cells containing disease specific targets. The ImmTACs enable circulating T-cells to selectively identify and kill diseased cells.

Durvalumab and tremelimumab are investigational immunotherapies of MedImmune, the global biologics research and development arm of AstraZeneca. Durvalumab is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. Durvalumab blocks these signals, countering the tumour’s immune-evading tactics. Tremelimumab is a fully human monoclonal IgG2 antibody which stimulates the immune system to destroy cancer cells through binding to the protein CTLA-4, expressed on the surface of activated T lymphocytes.

The open label, four arm, randomizsd Phase Ib/II trial will explore IMCgp100 paired respectively with durvalumab and tremelimumab as well as investigating all three immunotherapy agents together. The primary goal of the combination trials will be to assess the safety and efficacy of the different combinations. Immunocore is responsible for conducting the trial.

The ‘backbone’ of best-in-class combinations

Commenting on the announcement, Dr Christina Coughlin, Chief Medical Officer of Immunocore, said, “This collaboration with MedImmune offers an excellent opportunity to explore how IMCgp100, together with durvalumab and tremelimumab respectively, could form the backbone of a set of best-in-class combinations for the treatment of patients with metastatic melanoma.”

The companies announced the formation of this combination partnership in April 2015 and also have a pre-existing research collaboration and licensing agreement, announced in January 2014, to develop novel cancer therapies using Immunocore’s ImmTAC technology.