On October 20, 2016 TG Therapeutics, Inc. (NASDAQ:TGTX) reported the launch of a Phase 1/2 study to evaluate the safety and efficacy of TGR-1202, the Company’s oral PI3K delta inhibitor in combination with carfilzomib, the FDA-approved proteasome inhibitor, in patients with relapsed or refractory lymphoma (Press release, TG Therapeutics, OCT 20, 2016, View Source [SID1234515923]).

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The rationale for combining these two agents is based on extensive preclinical work conducted as part of a research collaboration supported by TG Therapeutics at the Center for Lymphoid Malignancies, Columbia University Medical Center. Portions of this work were presented in an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting in December 2015, by Dr. Changchun Deng of the Center for Lymphoid Malignancies. The presentation contained data demonstrating that the combination of TGR-1202 and carfilzomib was uniquely synergistic as compared to any other combination of a PI3K-delta inhibitor and proteasome inhibitor, including the combination of idelalisib and carfilzomib and idelalisib and bortezomib. Of particular interest, the combination of TGR-1202 and carfilzomib was found to potently inhibit cap dependent translation of c-Myc in all cell lines tested, including diffuse large B-Cell lymphoma (DLBCL), mantle cell lymphoma (MCL), multiple myeloma, T-cell lymphoma, and chronic lymphocytic leukemia (CLL) cells. A more in depth presentation of the preclinical work has been submitted to a leading medical journal and is awaiting publication.

In the Phase 1 portion, the study will evaluate the safety, tolerability, and appropriate dose of carfilzomib when combined with 800mg of TGR-1202. Once a recommended Phase 2 dose is identified, the Phase 2 portion will further evaluate the safety and effectiveness of the combination at the chosen dose. TG Therapeutics will supply the TGR-1202 and assume up to 50% for the cost for the trial.

"We are very excited about the launch of this combination study, building on the extensive preclinical work completed by Dr. Deng, Dr. Owen A. O’Connor and the team from Columbia Presbyterian Medical Center, allowing us to move the science from bench to bedside and into patients in need of combination therapies. TGR-1202 continues to exhibit best-in-class safety and efficacy results and has demonstrated itself as a uniquely combinable PI3k-delta inhibitor. Our hope is that combination therapies with TGR-1202 could significantly improve the outcomes for patients with lymphoma," stated Michael S. Weiss, the Company’s Executive Chairman and Interim Chief Executive Officer."

"C-myc continues to be one of the most challenging tumor mutations to target. C-myc tumors include some of the most difficult to treat, including double hit lymphoma and triple negative breast cancer, which are generally resistant to currently available therapies leading to very poor outcomes for patients. The work we completed at Columbia appears to identify a novel mechanism for targeting c-myc by combining these two agents and we are eager to see if the work in the lab translates into helping these patients. We look forward to working with TGR-1202 and carfilzomib in this important clinical research project," stated Dr. Owen O’Connor, Director Lymphoid Malignancies at Columbia Presbyterian Medical Center.

This study is currently open to enrollment at the Center for Lymphoid Malignancies, Columbia Presbyterian Medical Center, New York, NY. More information on this clinical study can be found at www.clinicaltrials.gov.