Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Entospletinib · 2 trials · 15 indications
The dose of obinutuzumab remains fixed in standard doses while the dose of entospletinib will be escalated. The starting dose of entospletinib will be 200 mg (twice-daily) and escalated to the second dose level 400 mg (twice-daily). MTD is the dose associated with a total of 6 patients treated with less than 2 dose limiting toxicities (DLT), or a total of 3 patients treated with less than 1 DLT. DLT is defined as 1) grade 3 or higher non-hematological toxicity (except grade 3 nausea, vomiting or diarrhea that was reversible within 72 hours with supportive care; grade 3 infusion-related toxicity; asymptomatic grade 3-4 laboratory abnormalities that are reversible to grade 2 or less within 72 hours; grade 3 tumor lysis syndrome or hyponatremia); 2) grade 4 neutropenia lasting \>7 days or febrile neutropenia; or 3) grade 4 thrombocytopenia/anemia or grade 3 thrombocytopenia with bleeding. The dosage follows the 3+3 traditional escalation rules.
Response for CLL/SLL measured using Modified International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 (IWCLL) guidelines. Response for hairy cell leukemia was measured using Consensus resolution: proposed criteria published in Leukemia 1987.
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Cmax is defined as the maximum concentration of drug.
| Arm | Type | Description |
|---|---|---|
| Treatment (entospletinib, obinutuzumab) | EXPERIMENTAL | Patients receive entospletinib PO either QD or BID on days -7 to -1 (run-in phase) depending on the assigned dose level. Patients also receive obinutuzumab IV on days 1, 2, 8, and 15 of the first cycle, and on day 1 of subsequent cycles. Treatment with obinutuzumab repeats every 28 days for up to 6 cycles and daily treatment with entospletinib continues every 28 days for up to 12 cycles in the absence of disease progression or unexpected toxicity. |
| Cohort 1 (Moderate Hepatic Impairment) | EXPERIMENTAL | Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| Cohort 2 (Severe Hepatic Impairment) | EXPERIMENTAL | Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| Cohort 3 (Mild Hepatic Impairment) | EXPERIMENTAL | Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5. |
| Name | Type | Description |
|---|---|---|
| Entospletinib | DRUG | Given PO |
| Laboratory Biomarker Analysis | OTHER | Correlative studies |
| Obinutuzumab | BIOLOGICAL | Given IV |
| Pharmacological Study | OTHER | Correlative studies |
Inclusion Criteria: * Phase I portion of the study: Histologically or flow cytometry confirmed diagnosis of B-CLL/SLL according to National Cancer Institute (NCI)-Working Group (WG) 1996 guidelines * Phase I portion of the study: The following types of NHL as documented by medical records and with ...
Entospletinib is an investigational small molecule being studied for use in oncology and anemia. It has been evaluated in clinical trials for conditions including relapsed chronic lymphocytic leukemia, small lymphocytic lymphoma, non-Hodgkin lymphoma, and related blood cancers, as well as for its pharmacokinetics in adults with normal and impaired liver function.
Entospletinib is a small molecule developed by Gilead Sciences. While its specific molecular target is not disclosed in the available information, it is being investigated as an oncology therapy. The drug has been studied in combination with obinutuzumab for certain lymphomas and leukemias.
Entospletinib is being developed by Gilead Sciences, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol GILD. The company has sponsored clinical trials of the drug in the United States, Germany, and New Zealand.
Entospletinib is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Two Phase 1 trials have been completed, one evaluating its pharmacokinetics in liver impairment and another testing it with obinutuzumab in patients with certain blood cancers.
Entospletinib has been studied in two completed Phase 1 trials. NCT02521376 evaluated its pharmacokinetics in 56 adults with normal and impaired liver function. NCT03010358 tested entospletinib with obinutuzumab in 24 patients with relapsed chronic lymphocytic leukemia, small lymphocytic lymphoma, or non-Hodgkin lymphoma.
No alternative names for Entospletinib have been reported. It is a distinct investigational small molecule developed by Gilead Sciences. In clinical trials, it has been studied as a single agent and in combination with obinutuzumab, but it is not known by any other drug name.