Date: 2016-04-19
Type of information: Clinical research agreement
Compound: guadecitabine and atezolizumab
Company: Astex Pharmaceuticals (UK) Genentech, a member of Roche Group (USA - CA - Switzerland)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism: enzyme inhibitor/DNA methyltransferase 1 (DNMT1) inhibitor/monoclonal antibody/immune checkpoint inhibitor. Guadecitabine is a novel next-generation, small molecule DNA hypomethylating agent formulated as a single, small volume, subcutaneous injection. The product was designed to deliver longer exposure to the active moiety, decitabine, compared to iv decitabine and more efficient delivery into key tissues, including the bone marrow. Guadecitabine demonstrated activity in restoring silenced tumor suppressor gene expression in cancer cells by reversal of DNA methylation and inducing responses in previously treated MDS and AML patients. Anti-PDL1 antibody MPDL3280A (atezolizumab) is an investigational monoclonal antibody designed to make cancer cells more vulnerable to the body’s immune system by interfering with a protein called PD-L1. PD-L1 is found on the surface of cells in tumours and is believed to act as a “stop sign,” preventing the immune system from destroying cancer cells. By inhibiting PD-L1, MPDL3280A may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells. MPDL3280A is being studied in clinical trials to understand whether blocking PD-L1 will help the immune system respond to cancer.
Disease: acute myeloid leukemia
Details: * On April 19, 2016, Astex Pharmaceuticals announced that it has entered into a clinical collaboration with Genentech. The collaboration will evaluate the potential for combining Astex’s guadecitabine (SGI-110), with Genentech’s anti-PD-L1 monoclonal antibody, atezolizumab, in the treatment of acute myeloid leukemia (AML). An initial Phase 1b study will investigate the safety and pharmacology of the combination. The collaboration will test the hypothesis that upfront “priming” of patients’ immune systems with guadecitabine, an epigenetic investigational drug, may result in enhanced responses to immunotherapy. The hypothesis is based on the observation that guadecitabine demethylates and induces re-expression of tumor associated antigens, as well as inducing or upregulating the expression of immune checkpoints such as programmed death 1 (PD-1), and programmed deathligand 1 (PD-L1) and 2 (PD-L2), rendering the tumor more immunogenic, and more susceptible to treatment with a checkpoint inhibitor antibody such as atezolizumab.
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