Date: 2014-07-29
Type of information: Clinical research agreement
Compound: indoleamine dioxygenase-1 (IDO1) inhibitor, INCB24360, and PD-L1 immune checkpoint inhibitor, MPDL3280A (atezolizumab),
Company: Genentech, a member of the Roche Group (USA - Switzerland) Incyte (USA - DE)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism: monoclonal antibody/immune checkpoint inhibitor/IDO1 inhibitor. INCB24360 is an orally bioavailable small molecule inhibitor of IDO1 (indoleamine dioxygenase-1) that has nanomolar potency in both biochemical and cellular assays, potent activity in enhancing T lymphocyte, dendritic cell and natural killer cell responses in vitro, with a high degree of selectivity. INCB24360 has been shown to be active in mouse models of cancer as a single agent and in combination with cytotoxic and immunotherapy agents, and its ability to reduce tumor growth is dependent on a functional immune system - consistent with its proposed mechanism of action. Preliminary clinical data from an ongoing Phase I/II trial evaluating INCB24360 in combination with the approved immunotherapy checkpoint inhibitor Yervoy® (ipilimumab) in metastatic melanoma, recently presented at the 50th Annual Meeting of the American Society of Clinical Oncology ( ASCO ), suggest anti-tumor synergy between the two agents, establishing proof of concept for the combination. Thus far, 42 percent of the immunotherapy-naïve patients receiving INCB24360 combined with ipilimumab achieved an objective response and 75 percent achieved disease control. In addition to the Phase I/II study in metastatic melanoma in combination with ipilimumab (NCT01604889), described in the ASCO presentation, Incyte has also established clinical research agreements to study INCB24360 in combination with the investigational anti-PD-1 immunotherapy checkpoint inhibitor MK-3475 (Merck), the investigational anti-PD-L1 immune checkpoint inhibitor MEDI4736 ( AstraZeneca /MedImmune), and the investigational anti-PD-1 immune checkpoint inhibitor nivolumab ( BMS). MPDL3280A (also known as anti-PDL1) is an investigational monoclonal antibody designed to interfere with PD-L1 (Programmed Death-Ligand 1). MPDL3280A is designed to make cancer cells more vulnerable to the body's own immune system by interfering with PD-L1. PD-L1 is expressed on tumor cells and tumor-infiltrating immune cells, preventing them from binding to two receptors, PD-1 and B7.1, on the surface of T cells. By inhibiting PD-L1, MPDL3280A may enable the activation of T cells, restoring their ability to effectively detect and attack tumor cells. The FDA has granted MPDL3280A Breakthrough Therapy Designation. This designation is designed to expedite the development and review of medicines intended to treat serious diseases and to help ensure patients have access to them through FDA approval as soon as possible.
Disease: non-small cell lung cancer (NSCLC)
Details: * On July 30, 2014, Incyte Corporation announced that it has entered into a clinical trial agreement with Genentech to evaluate the safety, tolerability and preliminary efficacy of Incyte's oral indoleamine dioxygenase-1 (IDO1) inhibitor, INCB24360, in combination with Genentech's PD-L1 immune checkpoint inhibitor, MPDL3280A, in patients with non-small cell lung cancer (NSCLC). Under the terms of the collaboration, Incyte and Genentech will collaborate on a non-exclusive basis to evaluate the combination of these immunotherapies. Incyte will be responsible for conducting the study and the results will be used to determine whether further clinical development of this combination is warranted. Further details of the agreement were not disclosed.
Financial terms:
Latest news:
