Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as RP5264, TGR-1202
Umbralisib · 8 trials · 19 indications
The CR Rate is defined as the proportion of participants achieving complete remission (CR) based on 2018 IW-CLL criteria.
ORR for MZL=percentage of participants with complete response (CR)/partial response (PR). ORR for WM=CR/PR/very good partial response (VGPR)/minor response (MR). Response assessed per revised Lugano Classification for MZL \&per IWWM for WM participants. Per Lugano criteria CR=complete disappearance of all evidence of disease \& disease-related symptoms. PR=regression of measurable disease \& no new disease sites. Regression=≥50% decrease in the sum of the products of the diameters (SPD) of index lesions, with no increase in size of other lymph nodes/liver/spleen.Per IWWM criteria CR=disappearance of serum monoclonal immunoglobulin M (IgM) protein by immunofixation with a normal serum IgM level. VGPR=reduction of monoclonal IgM protein \>90% from baseline. PR=reduction of monoclonal IgM protein between 50-90% from baseline with regression of measurable disease. Regression defined in similar manner as Lugano Classification. MR=reduction of monoclonal IgM protein \>25% but \<50% from baseline.
DOR is defined as the time from documentation of a response to treatment to the first documentation of tumor progression or death due to any cause, whichever comes first.
To assess the safety of TGR1202 in combination with ibrutinib relapsed or refractory CLL or MCL. DLT is based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. DLT refers to toxicities experienced at any time during the study treatment, defined as Grade 4 anemia; Grade 4 neutropenia lasting \>7 days (while receiving growth factor support); Grade 4 thrombocytopenia lasting \> 7 days; Grade ≥3 febrile neutropenia; and Grade ≥3 thrombocytopenia with Grade \>2 hemorrhage;Grade ≥ 3 non-hematologic toxicity unresponsive to standard supportive care measure with the exception of asymptomatic Grade ≥3 lab abnormalities that resolve to ≤ Grade 1 or baseline within 7 days;treatment delay of ≥14 days due to unresolved toxicity; and non-hematologic toxicity of Grade 2 (at any time during treatment) that, in the judgment of the Investigators, Study Chair, and the Medical Monitor, is dose-limiting.
To determine the incidence of adverse events, any potential abnormal laboratory results and any dose-limiting toxicities
To determine the incidence of adverse events, any potential abnormal laboratory results and any dose-limiting toxicities.
To determine the incidence of adverse events, any potential abnormal laboratory results and any dose-limiting toxicities
| Arm | Type | Description |
|---|---|---|
| Cohort 1-Relapsed Disease | EXPERIMENTAL | Participants with relapsed disease * Treatment with Acalabrutinib \& Umbralisib beginning C1D1, * Ublituximab beginning C7D1 * Assessment of treatment response * Treatment continues for a maximum of 24 cycles. Participants followed post treatment for a maximum of 5 years |
| Cohort 2-Treatment Naive | EXPERIMENTAL | Participants with previously untreated disease * Treatment with Acalabrutinib \& Umbralisib beginning C1D1, * Ublituximab beginning C7D1 * Assessment of treatment response * Treatment continues for a maximum of 24 cycles. Participants followed post treatment for a maximum of 5 years |
| Marginal Zone Lymphoma (MZL): Umbralisib | EXPERIMENTAL | Participants with non-follicular indolent non-Hodgkin's lymphoma (iNHL) with MZL as the histology type received umbralisib, 800 milligrams (mg), orally, once daily (QD), until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first. |
| Waldenstrom's Macroglobulinemia (WM): Umbralisib | EXPERIMENTAL | Participants with non-follicular iNHL with WM as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first. |
| CLL | EXPERIMENTAL | Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. * Each Cycle = 28 days * TGR-1202 (oral): Starting on Day 1 administered daily. * Ibrutinib (oral): Starting on Day 1 administered daily. |
| MCL | EXPERIMENTAL | Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. * Each Cycle = 28 days * TGR-1202 (oral): Starting on Day 1 administered daily. * Ibrutinib (oral): Starting on Day 1 administered daily. |
| TG-1501 + Ublituximab + Umbralisib | EXPERIMENTAL | Ublituximab at a fixed IV infusion dose Days 1, 8 and 15 followed by maintenance infusions Umbralisib oral daily dose TG-1501 IV infusion at scheduled intervals |
| TGR-1202 | EXPERIMENTAL | TGR-1202 daily dose |
| TGR-1202 + nab-paclitaxel + gemcitabine | EXPERIMENTAL | TGR-1202 oral daily dose + nab-paclitaxel + gemcitabine both as an IV infusion |
| TGR-1202 + FOLFOX | EXPERIMENTAL | TGR-1202 oral daily dose + oxaliplatin IV infusion + leucovorin IV infusion followed by 5-fluorouracil IV bolus followed by 5-FU IV infusion (FOLFOX regimen) |
| TGR-1202 + FOLFOX + Bevacizumab | EXPERIMENTAL | TGR-1202 oral daily dose + oxaliplatin IV infusion + leucovorin IV infusion followed by 5-fluorouracil IV bolus followed by 5-FU IV infusion (FOLFOX regimen) + bevacizumab IV infusion |
| TGR-1202 + brentuximab vedotin | EXPERIMENTAL | TGR-1202 oral daily dose in combination with a fixed IV infusion of brentuximab vedotin |
| TGR-1202 + Obinutuzumab + Chlorambucil | EXPERIMENTAL | TGR-1202 is an oral daily dose with obinutuzumab at a fixed IV infusion and chlorambucil as an oral dose on specified days. |
| Name | Type | Description |
|---|---|---|
| Acalabrutinib | DRUG | Oral, twice a day, predetermined dosage |
| Umbralisib | DRUG | Oral, once a day, predetermined dosage, each 28 day cycle up to 24 cycles |
| Ublituximab | DRUG | 28 day cycle, starting cycle 7 via iv, on at predetermined dosage and timepoints in each cycle |
| TGR-1202 | DRUG | Capsules taken whole daily with water and with food |
| Ibrutinib | DRUG | Capsules taken whole with water- Do not consume fish oil, vitamin E, grapefruit, or Seville oranges |
| TG-1501 | BIOLOGICAL | IV immunotherapy for cancer |
| nab-paclitaxel + gemcitabine | DRUG | IV infusion |
| Oxaliplatin + Folinic acid + Fluorouracil | DRUG | IV infusion |
| Oxaliplatin + Folinic acid + Fluorouracil + Bevacizumab | DRUG | IV Infusion |
| TGR-1202 + brentuximab vedotin | DRUG | TGR-1202 an oral daily dose with an IV infusion of brentuximab vedotin |
| TGR-1202 + Obinutuzumab + Chlorambucil | DRUG | TGR-1202: Oral dose Obinutuzumab: IV infusion Chlorambucil: Oral dose |
Inclusion Criteria: * Confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) per International Workshop on CLL (iwCLL) 2018 criteria.1 * Participants must have an indication for treatment as defined by iwCLL 2018 criteria.1 * Participants must have measurable ...
Umbralisib is an investigational small molecule kinase inhibitor being developed by TG Therapeutics, Inc. for hematologic cancers. It is being studied in chronic lymphocytic leukemia and marginal zone lymphoma, among other indolent non-Hodgkin's lymphomas. It has been evaluated in Phase 1 and Phase 2 clinical trials.
Umbralisib is being studied in chronic lymphocytic leukemia, including relapsed and refractory disease, and in combination with other agents such as acalabrutinib and ublituximab. It is also being evaluated in marginal zone lymphoma and other non-follicular indolent non-Hodgkin's lymphomas. It remains an investigational therapy in clinical development.
Umbralisib is an inhibitor of CSNK1E, PIK3CD, and ABL1. These are the molecular targets associated with the drug, and its activity is characterized as kinase inhibition across these targets. This target profile distinguishes it from agents that act on a single kinase.
Umbralisib is developed by TG Therapeutics, Inc., which trades on the Nasdaq under the ticker TGTX. The company is the sponsor of the clinical trials evaluating the drug in hematologic malignancies.
Umbralisib has been evaluated in Phase 1 and Phase 2 clinical trials. It is an investigational agent and is not described as FDA approved. Its development has covered chronic lymphocytic leukemia, marginal zone lymphoma, and related indolent non-Hodgkin's lymphomas.
Umbralisib has been studied in trials including NCT04624633, which evaluates acalabrutinib, umbralisib, and ublituximab in relapsed and untreated CLL, and NCT03364231, a completed Phase 2 study in non-follicular indolent non-Hodgkin's lymphoma. NCT02535286 studied immunotherapy with ublituximab and umbralisib in relapsed or refractory CLL or Richter's transformation.