Phase 1/2 Clinical Trial to Test Combination Therapy in Advanced Lymphomas

Phase 1/2 Clinical Trial to Test Combination Therapy in Advanced Lymphomas

TG Therapeutics has started a Phase 1/2 trial to evaluate the safety and efficacy of its PI3K delta inhibitor TGR-1202, in combination with the proteasome inhibitor carfilzomib, in patients with relapsed or refractory lymphoma.

The study (NCT02867618) is now enrolling patients at the Center for Lymphoid Malignancies, Columbia Presbyterian Medical Center, New York.

“We are very excited about the launch of this combination study,” Michael S. Weiss, TG Therapeutics’s executive chairman and interim chief executive office, said in a news release. “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.”

Carfilzomib, marketed as Kyprolis, is an FDA-approved proteasome inhibitor for the treatment of multiple myeloma patients who have received at least two prior therapies. Although not approved for lymphoma patients, extensive preclinical work, conducted as a collaboration between TG Therapeutics and the Center for Lymphoid Malignancies, has demonstrated a unique synergy when carfilzomib and TGR-1202 where combined in variety of lymphoma cell lines.

At a 2015 scientific conference, the new study’s lead investigator, Dr. Changchun Deng, reported that this combination was seen to be stronger than any other combination of a proteasome inhibitor and a PI3K-delta inhibitor, including that of idelalisib and bortezomib, or idelalisib and carfilzomib. The researchers found that TGR-1202 plus carfilzomib potently inhibited the production of the c-Myc protein in all cell lines tested. Those included diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), T-cell lymphoma, chronic lymphocytic leukemia (CLL), and multiple myeloma cells.

“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,” said Dr. Owen O’Connor, director of Lymphoid Malignancies at Columbia Presbyterian Medical Center. “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.”

The trial, which intends to enroll 42 patients with advanced non-Hodgkin’s lymphoma and Hodgkin’s lymphoma, will be conducted in two phases. In Phase 1, safety, tolerability, and the appropriate dose of carfilzomib will be assessed in combination with 800 mg TGR-1202. Then, when the best carfilzomib dose is identified, Phase 2 will evaluate the combination’s safety and efficacy. More information, including enrollment information, is available on the study’s clinical webpage.

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