TGR-1202 (umbralisib) is an investigational therapy being developed by TG Therapeutics for the treatment of several hematologic cancers (cancers which form in the blood or immune system) and autoimmune diseases (diseases which result from an immune reaction against the body’s own cells or tissues).

How TGR-1202 works

TGR-1202 is a phosphoinositide 3-kinase (PI3K) delta inhibitor, which means that it blocks the delta variant of PI3K, a type of enzyme that is present on the surface of healthy cells and cancer cells and whose role is to transmit signals between cells to help control their growth.

Some cancers have very large amounts of PI3K, which plays a key role in tumor cell regulation and survival.

When TGR-1202 binds to the delta variant of PI3K found on tumor cells, it prevents the activation of a cascade of signals that leads to their uncontrolled growth and survival.

Importantly, TGR-1202 does not affect the normal function of PI3K in healthy, non-cancer cells, as it seems that, unlike normal cells, cancer cells are “addicted” to oncogenic PI3K signaling and will be preferentially impacted by this treatment.

TGR-1202 in clinical trials

TGR-1202 is in clinical development for several blood cancers as a single therapy and in combination with other therapies.

The activity of TGR-1202 in combination with Adcetris (brentuximab vedotin) was investigated in cell lines of Hodgkin’s lymphoma in the laboratory, with positive results: TGR-1202 was shown to increase the anti-tumor activity of Adcetris, leading to tumor-killing effects in Hodgkin’s lymphoma.

Results from a Phase 1 trial (NCT02006485) with TGR-1202 were presented at the 2017 Annual Meeting of the American Society of Clinical Oncology (Abstract 7511) and at the 2017 European Hematology Association Congress (Abstract S772) in patients with advanced chronic lymphocytic leukemia and other subtypes of non-Hodgkin’s lymphoma.

This trial tested TGR-1202 in combination with two other therapies, TG-1101 (ublituximab) and Imbruvica (ibrutinib), and showed that the triple combination was clinically effective and tolerable in patients.

Of the 36 patients evaluated with several subtypes of non-Hodgkin’s lymphoma, 83 percent responded to treatment. All 19 patients with chronic lymphocytic leukemia and small lymphocytic lymphoma responded to treatment, with six patients showing a complete response. The triple combo was well tolerated, with most adverse effects being mild (grades 1 or 2). Responses were durable, with patients staying on the therapy for 11 months or longer.

In November 2017, TG Therapeutics announced the beginning of a Phase 2 trial (NCT03269669) of TGR-1202 in follicular lymphoma in collaboration with SWOG, the global cancer clinical trials group funded by the National Cancer Institute (NCI).

This trial will evaluate six cycles of treatment with the combination of TGR-1202 plus Gazyva (obinutuzumab) in follicular lymphoma grade 1, 2, and 3a. The study is now open and recruiting participants at over 100 clinical sites across the U.S.

TG-1202 is also in Phase 3 clinical development in combination with TG-1101 in patients with various hematologic cancers after the combination was proven effective in a Phase 2b clinical trial.

A Phase 1 clinical trial (NCT03283137) was initiated in September 2017 to assess the combination of TGR-1202 with the immunotherapy Keytruda (pembrolizumab) in patients with advanced chronic lymphocytic leukemia and B-cell non-Hodgkin’s lymphoma. This study is recruiting participants at the University of Chicago, which is also its sponsor.


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