Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as ENTO, GS 9973
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 ...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Bristol-Myers Squibb Company | BMY | 2 | PHASE3 | Luspatercept |
| Takeda Pharmaceutical Co. Ltd. Sponsored ADR | TAK | 2 | PHASE3 | Elritercept |
| Disc Medicine, Inc. | IRON | 2 | PHASE2 | DISC-0974 |
| Akebia Therapeutics, Inc. | AKBA | 2 | PHASE3 | Vadadustat |
| Ascentage Pharma Group International Unsponsored ADR | AAPG | 1 | PHASE1 | APG-5918 |
| Bayer | BAYRY | 1 | - | Molidustat |
Entospletinib is an investigational small molecule SYK inhibitor developed by Gilead Sciences, Inc. (ticker GILD). It has been studied in Phase 1 clinical trials in oncology and anemia settings, including hematologic malignancies such as chronic lymphocytic leukemia, small lymphocytic lymphoma, and non-Hodgkin lymphoma.
Entospletinib targets SYK, a spleen tyrosine kinase, and acts as an inhibitor of this molecular target. By inhibiting SYK, the drug is designed to interfere with B-cell receptor signaling pathways relevant to certain blood cancers and immune conditions.
Entospletinib is developed by Gilead Sciences, Inc., which trades under the ticker GILD. Gilead is the sponsor behind the clinical development program for this SYK inhibitor.
Entospletinib is in Phase 1 clinical development. It is investigational and has been evaluated in early-stage trials, including a completed Phase 1 study of entospletinib plus obinutuzumab in relapsed blood cancers and a completed Phase 1 pharmacokinetic study in adults with normal and impaired liver function.
Entospletinib has been studied in completed Phase 1 trials including NCT03010358, which combined entospletinib with obinutuzumab in relapsed chronic lymphocytic leukemia, small lymphocytic lymphoma, or non-Hodgkin lymphoma, and NCT02521376, a pharmacokinetic study in adults with normal and impaired liver function.
Entospletinib has been investigated for hematologic cancers including chronic lymphocytic leukemia, small lymphocytic lymphoma, non-Hodgkin lymphoma, and related B-cell malignancies, as well as anemia. It remains investigational and is not established as an approved therapy for these conditions.