Date: 2017-01-04
Type of information: Initiation of the trial
phase: 2
Announcement: initiation of the trial
Company: TG Therapeutics (USA - NY) National Cancer Institute (NCI) (USA)
Product: TGR-1202 plus ibrutinib
Action
mechanism: Bruton tyrosine kinase inhibitor/phosphoinositide 3-kinase (PI3K) inhibitor TGR-1202 (formerly known as RP5264) is an orally available PI3K delta inhibitor, targeting the delta isoform with nanomolar potency and several fold selectivity over the alpha, beta, and gamma isoforms of phosphoinositide 3-kinase. The delta isoform of PI3K is strongly expressed in cells of hematopoietic origin and is believed to be important in the proliferation and survival of B-cell lymphocytes. Inhibition of PI3K delta signaling with TGR-1202 has demonstrated robust activity in numerous pre-clinical models and primary cells from patients with hematologic malignancies. Ibrutinib is a novel Bruton’s tyrosine kinase (BTK) inhibitor being jointly developed by Janssen and Pharmacyclics, Inc. for the treatment of B-cell malignancies. Ibrutinib is jointly developed and commercialized in the United States by Pharmacyclics and Janssen Biotech, Inc. In Europe, Janssen-Cilag International NV (Janssen) holds the marketing authorization and its affiliates market Imbruvica® in EMEA (Europe, Middle East, Africa), as well as the rest of the world. Imbruvica® is already approved in Europe to treat adult patients with relapsed or refractory mantle cell lymphoma (MCL) and adult patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy or in first line use in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy. The rationale for combining these two agents is based on the prior clinical activity and tolerable safety profile observed with TGR-1202 both alone and in combination with ibrutinib in previous studies, as well as preclinical work conducted as part of a research collaboration with Dr. Michael Green and the University of Nebraska Medical Center's Lymphoma Precision Medicine Laboratory in Omaha, NE. The combination of TGR-1202 and ibrutinib has been studied previously in patients with Chronic Lymphocytic Leukemia (CLL) and non-Hodgkin's lymphoma, both with and without the addition of the anti-CD20 monoclonal antibody TG-1101 (ublituximab). Data on the combination of TGR-1202 plus ibrutinib were presented most recently at the 2016 American Society of Hematology (ASH) meeting, with data demonstrating an acceptable safety profile at full doses of both ibrutinib and TGR-1202.
Disease: diffuse large B-cell lymphoma (DLBCL)
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This phase IIa trial studies the side effects and how well TGR-1202 and ibrutinib work in treating patients with diffuse large B-cell lymphoma that has returned after a period of improvement or does not respond to treatment. TGR-1202 and ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. (NCT02874404)
Latest
news: * On January 4, 2017, TG Therapeutics announced the opening of an investigator initiated Phase 2 study at the University of Nebraska Medical Center (UNMC) to evaluate the safety and efficacy of TGR-1202, the Company's oral PI3K delta inhibitor in combination with ibrutinib, in patients with relapsed or refractory Diffuse Large B-cell Lymphoma (DLBCL). TG Therapeutics and Janssen Pharmaceuticals will each provide drug and equally share study-related costs. The Phase 2 study will evaluate the safety and efficacy of the combination of TGR-1202 and ibrutinib, as well as explore correlative analyses related to the combination.
