Date: 2016-01-20
Type of information: Initiation of the trial
phase: 1-2
Announcement: initiation of the trial
Company: Immunocore (UK) MedImmune (USA - global biologics arm of AstraZeneca (UK) Inovio Pharmaceuticals (USA - PA)
Product: IMCgp100, durvalumab (MEDI4736) and tremelimumab
Action
mechanism: cell therapy/gene therapy/immunotherapy product/monoclonal antibody/immune checkpoint inhibitor. IMCgp100 is a bispecific biologic known as a T cell redirector. It is incorporating an engineered T cell receptor (TCR) specific for a peptide antigen derived from the protein gp100 presented in the context of HLA A2 on the surface of melanoma cells. The TCR is fused to an anti-CD3 scFv fragment that recruits and activates non-melanoma specific T cells (killer T cells) in physical contact with the cancer T cell. IMCgp100 binds, with picomolar affinity, to a melanoma associated target, gp100; once bound Durvalumab (MEDI4736) is a human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. MEDI4736 blocks these signals, countering the tumour’s immune-evading tactics. This antibody is directed against B7-H1, have been shown to block the interaction between B7-H1 and its receptors, PD-1 and CD80 (B7-1). This blockade may help to overcome the immunosuppressive effects of B7-H1 on anti-tumor T cells. Tremelimumab is a fully human monoclonal antibody which binds to the protein CTLA-4, expressed on the surface of activated T lymphocytes.
IMCgp100 redirects all T cells, including non-cancer specific T cells, to kill the cancer cells.
Disease: melanoma
Therapeutic area: Cancer - Oncology
Country: Germany, UK, USA
Trial
details: This study is a Phase Ib/II, multi-center, open-label study of IMCgp100 as a single agent and in combination with durvalumab (MEDI4736) and/or tremelimumab in metastatic cutaneous melanoma. The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of IMCgp100 in combination with durvalumab (MEDI4736, programmed death-ligand 1 [PD-L1] inhibitor), tremelimumab (CLTA-4 inhibitor), and the combination of durvalumab with tremelimumab compared to single-agent IMCgp100 alone. The study will enroll patients who have metastatic melanoma that is refractory to treatment with an anti-PD-1 inhibitor as well as patients naive to therapy in the metastatic setting. Recent biologic evidence indicates that optimal responses to programmed cell death-1 (PD-1) directed therapy require the presence of CD8+ T cells in the tumor microenvironment and thus therapies such as IMCgp100 that recruit these effector cells to the tumor may overcome pre-existing resistance to checkpoint blockade. This emerging biology of checkpoint inhibitor resistance suggests the combination of IMCgp100 with checkpoint inhibition may have enhanced activity in patients with pre-existing resistance. (NCT02535078)
Latest
news: * On January 20, 2016, Immunocore announced that it has started a Phase Ib/II combination trial for the treatment of metastatic cutaneous melanoma. The trial will evaluate IMCgp100, Immunocore’s lead ImmTAC (Immune Mobilising Monoclonal T-Cell Receptor Against Cancer), in combination with durvalumab and The open label, four arm, randomized 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.
tremelimumab of MedImmune, the global biologics research and development arm of AstraZeneca.
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 technolog
