TG Therapeutics is starting a Phase 2 clinical trial evaluating the safety and efficacy of its oral PI3K delta inhibitor, TGR-1202, in combination with Imbruvica (ibrutinib) to treat relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
The single-center Phase 2 clinical trial (NCT02874404) will explore side effects and how well the combination works for DLBCL patients whose cancer has returned after a period of improvement or does not respond to treatment. It will be conducted at the University of Nebraska Medical Center.
Results from preclinical studies — conducted as part of a research partnership with Michael Green, PhD, and the University of Nebraska Medical Center’s Lymphoma Precision Medicine Laboratory in Omaha — provided the basis to test the combo in DLBCL patients.
The TGR-1202-Imbruvica combo has been tested in patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma, both alone and in combination with TG-1101 (ublituximab), an anti-CD20 monoclonal antibody.
During the 2016 American Society of Hematology (ASH), TG Therapeutics presented a positive safety profile of the TGR-1202-Imbruvica combo therapy, with both drugs at full doses.
“We are excited to launch this study led by Drs. Matthew Lunning and Michael Green. Dr. Lunning has extensive experience treating lymphoma patients with TGR-1202 as a doublet in combination with TG-1101 and also as a triple therapy with ibrutinib. While the triple combination appears safe, well tolerated and active, looking at the effects of the all oral doublet combination will expand our understanding of the effects of these agents together and the contribution of TG-1101 in a triple combination,” Michael S. Weiss, the company’s executive chairman and interim chief executive officer, said in a press release.
TGR-1202 is an orally available PI3K delta inhibitor. PI3K is expressed in cells of hematopoietic origin and is believed to be important in the increase and survival of B-cell lymphocytes.
Imbruvica is a small molecule drug that binds permanently to a protein called Bruton’s tyrosine kinase, which is important in B-cells. The drug is used to treat B-cell cancers such as mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström’s macroglobulinemia, a form of non-Hodgkin’s lymphoma.
Medication for the study will be provided by TG Therapeutics and Janssen Pharmaceuticals, and the companies will share the study-related costs.