Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as RP5264, Umbralisib, UKONIQ
TGR-1202 · 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 ...
TGR-1202 is an investigational small molecule PI3K-delta inhibitor developed by TG Therapeutics, Inc. (TGTX). It has been studied in Phase 1 clinical trials, both as a single agent and in combination regimens, across hematologic malignancies and select solid tumors, including chronic lymphocytic leukemia, lymphoma, and pancreatic cancer.
TGR-1202 has been studied in chronic lymphocytic leukemia and chronic lymphocytic leukemia/small lymphocytic lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and pancreatic cancer. These programs were Phase 1 investigations, and TGR-1202 is not an approved therapy for any of these indications.
TGR-1202 targets PI3K-delta, a kinase in the phosphoinositide 3-kinase family. It is a small molecule kinase inhibitor directed at the delta isoform of PI3K, a signaling enzyme implicated in B-cell malignancies, which is the rationale for its study in chronic lymphocytic leukemia and lymphoma.
TGR-1202 is developed by TG Therapeutics, Inc., which trades on the Nasdaq under the ticker TGTX. The company sponsored the Phase 1 studies of TGR-1202 as a single agent and in combination with other agents in hematologic cancers and select solid tumors.
TGR-1202 is in Phase 1 development. Its clinical program consists of completed Phase 1 and Phase 1/1b studies, and it is an investigational agent rather than an FDA-approved product. No active trials of TGR-1202 are currently listed.
Completed TGR-1202 trials include NCT02574663 in relapsed or refractory solid tumors including pancreatic cancer, NCT02268851 with ibrutinib in CLL or mantle cell lymphoma, NCT02164006 with brentuximab vedotin in Hodgkin's lymphoma, and NCT02100852 with obinutuzumab and chlorambucil in CLL.