Safety and Efficacy of the Combination of Tirabrutinib and Entospletinib With and Without Obinutuzumab in Adults With Chronic Lymphocytic Leukemia (CLL)
CompletedPhase 2Results postedLast updated 21 December 2021
What this trial tests
Phase 2 trial testing Tirabrutinib in Chronic Lymphocytic Leukemia in 36 participants. Completed in 1 October 2020.
18 and older, any sex, with Chronic Lymphocytic Leukemia. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Rate of Complete Remission/Complete Remission With Incomplete Recovery of the Bone Marrow (CR/CRi), as Assessed by Investigator Using Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria at Week 25Primary· Week 25
Rate of CR per modified IWCLL 2008 criteria at Week 25 was defined as the percentage of participants who achieved CR/complete remission with incomplete recovery of the bone marrow (CRi) at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy \> 1.5 cm/hepatomegaly/splenomegaly; lymphocytes \< 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets \> 100,000/µL; hemoglobin \> 11 g/dL; and neutrophils \> 1500/µL. CRi: CR criteria (no lymphadenopathy \> 1.5 cm/hepatomegaly/splenomegaly; lymphocytes \< 4000
Group
Value
95% CI
Tirabrutinib + Entospletinib
0
0 – 39.3
Tirabrutinib + Entospletinib + Obinutuzumab
6.7
1.2 – 19.5
Rate of CR With Bone Marrow Minimal Residual Disease (CR/BM MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25Secondary· Week 25
Rate of CR/BM MRD at Week 25 was defined as percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved BM MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy \> 1.5 cm/hepatomegaly/splenomegaly; lymphocytes \< 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets \> 100,000/µL; hemoglobin \> 11 g/dL; and neutrophils \> 1500/µL. CRi: CR criteria (no lymphadenopathy \> 1.5 cm/hepatomegaly/splenomegaly; lymphocytes \< 4000/μL; bone marrow \[hypocel
Group
Value
95% CI
Tirabrutinib + Entospletinib
0
0 – 39.3
Tirabrutinib + Entospletinib + Obinutuzumab
3.3
0.2 – 14.9
Rate of CR With Peripheral Minimal Residual Disease (CR/PB MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25Secondary· Week 25
Rate of CR/PB MRD at Week 25 was defined as the percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved PB MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy \> 1.5 cm/hepatomegaly/splenomegaly; lymphocytes \< 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets \> 100,000/µL; hemoglobin \> 11 g/dL; and neutrophils \> 1500/µL. CRi: CR criteria (no lymphadenopathy \> 1.5 cm/hepatomegaly/splenomegaly; lymphocytes \< 4000/μL; bone marrow \[hyp
Group
Value
95% CI
Tirabrutinib + Entospletinib
0
0 – 39.3
Tirabrutinib + Entospletinib + Obinutuzumab
3.3
0.2 – 14.9
Overall Response Rate (ORR), as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25Secondary· Week 25
ORR was assessed based on modified IWCLL 2008 criteria and was defined as percentage of participants achieving a CR, CRi, partial remission (PR; including nodular partial response \[nPR\]), and PR with lymphocytosis (PR-L). CR and CRi: meeting all the criteria that have been defined in Outcome measures 1, 2 and 3. PR: ≥ 2 of these: ≥ 50% decrease in lymphocytes, lymphadenopathy, size of liver, size of spleen, and 50% decrease in bone marrow infiltrates; and ≥ 1 of these: neutrophils \> 1500/μL or ≥ 50% increase from Baseline, platelets ≥ 100,000/µL or ≥ 50% increase from Baseline, hemoglobin \
Group
Value
95% CI
Tirabrutinib + Entospletinib
100.0
60.7 – 100.0
Tirabrutinib + Entospletinib + Obinutuzumab
90.0
76.1 – 97.2
Percentage of Participants Experiencing Any Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)Secondary· First dose date up to the last dose date (maximum: 105.9 weeks) plus 30 days
A treatment emergent AE is defined as an AE that occurs or worsens in severity on or after the date of the first dose of study drug but no later than 30 days after the permanent discontinuation of study drug or an AE leading to discontinuation of study drug. A SAE is defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction.
Any Treatment-Emergent AEs
Group
Value
95% CI
Tirabrutinib + Entospletinib
100.0
Tirabrutinib + Entospletinib + Obinutuzumab
100.0
Treatment-Emergent SAEs
Group
Value
95% CI
Tirabrutinib + Entospletinib
16.7
Tirabrutinib + Entospletinib + Obinutuzumab
50.0
Adverse events — posted to ClinicalTrials.gov
Time frame: Adverse Events: First dose date up to last dose date (maximum: 105.9 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 42 months.
Reporting threshold: 5%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
The primary objective of this study is to determine the preliminary efficacy of the combination of tirabrutinib (formerly GS-4059) and entospletinib with obinutuzumab in adults with relapsed or refractory chronic lymphocytic leukemia (CLL).
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
NCT07198087 — A Study to Investigate the Pharmacokinetics of Tirabrutinib in Participants With Mild, Moderate, and Severe Hepatic Impa
· Phase 1
· active not recruiting
NCT04947319 — Study of Tirabrutinib (ONO-4059) in Patients With Primary Central Nervous System Lymphoma (PROSPECT Study)
· Phase 2
· active not recruiting
NCT03100942 — Study to Assess Safety and Efficacy of Filgotinib, Lanraplenib and Tirabrutinib in Adults With Active Sjogren's Syndrome
· Phase 2
· completed
NCT02968563 — Study to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib and Idelalisib With and Without Obinutuzuma
· Phase 2
· completed
NCT02626026 — Study to Evaluate Safety and Pharmacokinetics of GS-4059 (Tirabrutinib) in Healthy Volunteers and Participants With Rheu
· Phase 1
· completed
Other recruiting trials for Chronic Lymphocytic Leukemia
Currently open trials in the same condition.
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· Phase 1
· recruiting
NCT06863402 — Nemtabrutinib and Pembrolizumab for the Treatment of Richter Transformation, Diffuse Large B-cell Lymphoma Subtype
· Phase 2
· recruiting
NCT07218510 — Venetoclax and Obinutuzumab Followed by Epcoritamab for the Treatment of Untreated Chronic Lymphocytic Leukemia and Smal
· Phase 2
· recruiting
NCT07288515 — Observ Prosp Study of Acalabrutinib in CLL Therapy in Real Clinical Practice in Belarus
· recruiting
NCT07014917 — Intermittent Versus Continuous Venetoclax With Acalabrutinib for CLL/SLL
· Phase 2
· recruiting
Other Gilead Sciences trials
Trials by the same sponsor.
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NCT06683482 — A Qualitative Study on Advanced Breast Cancer Patients and Their Caregivers in Spain
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NCT06613685 — Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated
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NCT06585150 — Study of Obeldesivir to Treat Nonhospitalized Adults With Acute Respiratory Syncytial Virus (RSV) Infection
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Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
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Sponsor: as reported to ClinicalTrials.gov by Gilead Sciences
Last refreshed: 21 December 2021
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