Date: 2015-09-25
Type of information: Clinical research agreement
Compound: epacadostat and CRS-207
Company: Aduro Biotech (USA - CA) Incyte (USA - DE)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism: enzyme inhibitor/immunotherapy product. Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been shown to induce regulatory T cell generation and activation, and allow tumors to escape immune surveillance. Epacadostat is an orally bioavailable small molecule inhibitor of IDO1 that has nanomolar potency in both biochemical and cellular assays and has demonstrated potent activity in enhancing T lymphocyte, dendritic cell and natural killer cell responses in vitro, with a high degree of selectivity. Epacadostat has shown proof-of-concept clinical data in patients with unresectable or metastatic melanoma in combination with the CTLA-4 inhibitor ipilimumab, and is currently in four proof-of-concept clinical trials with PD-1 and PD-L1 immune checkpoint inhibitors in a variety of cancer types. CRS-207 is one of a family of product candidates based on Aduro's live-attenuated, double-deleted (LADD) Listeria monocytogenes immuno-oncology platform that are designed to induce potent innate and adaptive immune responses. CRS-207 has been engineered to express the tumor-associated antigen mesothelin, which is over-expressed in many cancers including mesothelioma and pancreatic, non-small cell lung, ovarian and gastric cancers.
Disease: ovarian cancer
Details: * On September 9, 2015, Aduro Biotech announced that it has entered into a clinical trial agreement with Incyte to evaluate the safety, tolerability and preliminary efficacy of Aduro's lead LADD immunotherapy, CRS-207, in combination with Incyte's oral indoleamine dioxygenase 1 (IDO1) inhibitor, epacadostat (INCB24360), in patients with ovarian cancer. The combination of both investigational immunotherapeutic agents, which have different but complementary mechanisms directed at enhancing the body's own immune defenses, may provide unique synergies in fighting cancer. Incyte's epacadostat has been shown in vitro and in preclinical tumor models to enhance activities of multiple types of immune cells by reducing the immune suppression characteristic of the tumor microenvironment. Aduro's CRS-207 has been shown to stimulate immune cell activity, with particular targeting mechanisms that seek and attack tumor cells that express mesothelin like those found in ovarian cancer. The Phase 1/2 trial, which is being funded equally between the two companies, is designed to test combinations of CRS-207 with two dose levels of epacadostat in dose escalation and then will expand to a Phase 2 evaluating the combination at the optimal dose level compared to CRS-207 alone based on safety and tumor biomarkers. The study plans to enroll up to 40 patients in Phase 1 and up to 86 patients in Phase 2 with platinum-resistant ovarian, fallopian or peritoneal cancers. The trial is expected to begin enrolling patients in early 2016. Under the terms of the collaboration, Aduro and Incyte will collaborate on a non-exclusive basis to evaluate the combination. Aduro will be responsible for conducting the study and the results will be used to determine whether further clinical development of this combination is warranted.
Financial terms: * On March 24, 2016, Aduro Biotech announced that the first patient has been dosed in SEASCAPE, the Phase 1/2 clinical study designed to evaluate the safety, tolerability and preliminary efficacy of CRS-207, Aduro’s lead listeria-based immunotherapy construct (LADD), in combination with epacadostat (INCB24360), Incyte Corporation’s selective IDO1 inhibitor, in patients with ovarian cancer.
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