Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as GS-4059, ONO-4059
Tirabrutinib · 5 trials · 5 indications
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/μL; bone marrow \[hypocellular\] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity.
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/μL; bone marrow \[hypocellular\] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity.
An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Treatment-emergent adverse events (TEAEs) were defined as 1 or both of the following: Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and/or Any AEs leading to premature discontinuation of study drug.
A treatment-emergent laboratory abnormality was defined as an increase of at least 1 abnormality grade from the predose assessment after the first dose of study drug and within 30 days after last study drug administration. Laboratory abnormalities without clinical significance were not recorded as AEs or serious AEs. Treatment-emergent laboratory abnormalities were graded per Common Terminology Criteria for Adverse Events (CTCAE), version 4.03 where 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = potentially life threatening.
Cmax is maximum observed concentration of drug in plasma.
Clast is the last observed concentration of drug in plasma.
Tmax is the time observed for the Cmax of tirabrutinib.
Tlast is the time observed for the Clast of tirabrutinib.
AUC is concentration of drug over time (area under the plasma concentration versus time curve).
AUC is concentration of drug over time (area under the plasma concentration versus time curve).
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as 1 or both of the following: Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and/or Any AEs leading to premature discontinuation of study drug.
A treatment-emergent laboratory abnormality was defined as an increase of at least 1 abnormality grade from the predose assessment after the first dose of study drug and within 30 days after last study drug administration. Laboratory abnormalities without clinical significance were not recorded as AEs or serious AEs. Treatment-emergent laboratory abnormalities were graded per CTCAE, version 4.03 where 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = potentially life threatening.
Treatment-emergent AEs were defined as one or both of the following: * Any AEs with an onset date on or after the study drug start date of parent study and no later than 30 days after permanent discontinuation of study drug in this rollover study; * Any AEs leading to premature discontinuation of study drug.
Treatment-emergent marked laboratory abnormalities were defined as values that increase from baseline by at least 3 toxicity grades at any postbaseline time point, up to and including the date of the last dose of study drug plus 30. If the relevant baseline laboratory value is missing, any Grade 3 or 4 values observed within the timeframe specified above will be considered treatment-emergent marked abnormalities. Laboratory assessments included tests for Chemistry, Hematology, Coagulation and Urinalysis.
Dose Limiting Toxicities (DLT) were defined as follows: * All Common Terminology Criteria (CTC) Grade 4 tirabrutinib related adverse events * All CTC Grade 3 tirabrutinib related adverse events, with the exception of the following: * CTC Grade 3 lymphocytosis considered an expected outcome of therapy Any toxicity which in the opinion of the Investigator is attributed to a participant's underlying disease was not considered a DLT.
| Arm | Type | Description |
|---|---|---|
| Tirabrutinib + Entospletinib | EXPERIMENTAL | Participants will receive tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) + entospletinib 400 mg (2 x 200 mg tablets) for up to 104 weeks. |
| Tirabrutinib + Entospletinib + Obinutuzumab | EXPERIMENTAL | Participants will receive tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) + entospletinib 400 mg (2 x 200 mg tablets) for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses on Day 1 of Weeks 2, 3, 5, 9, 13, 17 and 21. |
| Tirabrutinib + Idelalisib | EXPERIMENTAL | Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) once daily + idelalisib 100 mg (1 x 100 mg tablet) once daily for up to 104 weeks. |
| Tirabrutinib + Idelalisib + Obinutuzumab | EXPERIMENTAL | Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) once daily + idelalisib 100 mg (1 x 100 mg tablet) once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses on Day 1 of Weeks 2, 3, 5, and then every 4 weeks through Week 21. |
| Cohort 1, Part A: Tirabrutinib 20 mg QD | EXPERIMENTAL | Tirabrutinib 20 mg capsules orally once daily (QD) in the morning for 1 week. |
| Cohort 1, Part A: Placebo | PLACEBO_COMPARATOR | Placebo to match tirabrutinib capsules orally QD in the morning for 1 week. |
| Cohort 2, Part A: Tirabrutinib 10 mg BID | EXPERIMENTAL | Tirabrutinib 10 mg capsules orally twice daily (BID) (morning and approximately 12 hours later) for 7 days. On Day 7, only morning dose was administered. |
| Cohort 2, Part A: Placebo | PLACEBO_COMPARATOR | Placebo to match tirabrutinib capsules orally BID (morning and approximately 12 hours later) for 7 days. On Day 7, only morning dose was administered. |
| Part B: Tirabrutinib 20 mg QD | EXPERIMENTAL | Tirabrutinib 20 mg capsules orally QD for 4 weeks. |
| Part B: Placebo | PLACEBO_COMPARATOR | Placebo to match tirabrutinib capsules orally QD for 4 weeks. |
| Tirabrutinib 40 mg once daily (CLL) | EXPERIMENTAL | Participants with relapsed/refractory chronic lymphocytic leukemia (CLL) received tirabrutinib 40 mg once daily for up to 96 months from first dose in the parent study. |
| Tirabrutinib 80 mg once daily (CLL) | EXPERIMENTAL | Participants with relapsed/refractory CLL received tirabrutinib 80 mg once daily for up to 96 months from first dose in the parent study. |
| Tirabrutinib 160 mg once daily (CLL) | EXPERIMENTAL | Participants with relapsed/refractory CLL received tirabrutinib 160 mg once daily for up to 96 months from first dose in the parent study. |
| Tirabrutinib 320 mg once daily (CLL) | EXPERIMENTAL | Participants with relapsed/refractory CLL received tirabrutinib 320 mg once daily for up to 96 months from first dose in the parent study. |
| Tirabrutinib 400 mg once daily (CLL) | EXPERIMENTAL | Participants with relapsed/refractory CLL received tirabrutinib 400 mg once daily for up to 96 months from first dose in the parent study. |
| Tirabrutinib 500 mg once daily (CLL) | EXPERIMENTAL | Participants with relapsed/refractory CLL received tirabrutinib 500 mg once daily for up to 96 months from first dose in the parent study. |
| Tirabrutinib 600 mg once daily (CLL) | EXPERIMENTAL | Participants with relapsed/refractory CLL received tirabrutinib 600 mg once daily for up to 96 months from first dose in the parent study. |
| Tirabrutinib 300 mg twice daily (CLL) | EXPERIMENTAL | Participants with relapsed/refractory CLL received tirabrutinib 300 mg twice daily for up to 96 months from first dose in the parent study. |
| Tirabrutinib 160 mg once daily (NHL) | EXPERIMENTAL | Participants with relapsed/refractory non-Hodgkin's lymphoma (NHL) received tirabrutinib 160 mg once daily for up to 96 months from first dose in the parent study. |
| Tirabrutinib 320 mg once daily (NHL) | EXPERIMENTAL | Participants with relapsed/refractory NHL received tirabrutinib 320 mg once daily for up to 96 months from first dose in the parent study. |
| Tirabrutinib 480 mg once daily (NHL) | EXPERIMENTAL | Participants with relapsed/refractory NHL received tirabrutinib 480 mg once daily for up to 96 months from first dose in the parent study. |
| Tirabrutinib 600 mg once daily (NHL) | EXPERIMENTAL | Participants with relapsed/refractory NHL received tirabrutinib 600 mg once daily for up to 96 months from first dose in the parent study. |
| Tirabrutinib 20 mg Once Daily (CLL) | EXPERIMENTAL | Participants with relapsed/refractory chronic lymphocytic leukaemia (CLL) received tirabrutinib 20 mg once daily. |
| Tirabrutinib 20 mg Once Daily (NHL) | EXPERIMENTAL | Participants with relapsed/refractory non-Hodgkin's lymphoma (NHL) received tirabrutinib 20 mg once daily. |
| Tirabrutinib 40 mg Once Daily (NHL) | EXPERIMENTAL | Participants with relapsed/refractory NHL received tirabrutinib 40 mg once daily. |
| Tirabrutinib 80 mg Once Daily (NHL) | EXPERIMENTAL | Participants with relapsed/refractory NHL received tirabrutinib 80 mg once daily. |
| Tirabrutinib 240 mg Twice Daily (NHL) | EXPERIMENTAL | Participants with relapsed/refractory NHL received tirabrutinib 240 mg twice daily. |
| Name | Type | Description |
|---|---|---|
| Tirabrutinib | DRUG | Administered orally once daily |
| Entospletinib | DRUG | Administered orally once daily |
| Obinutuzumab | DRUG | Administered intravenously |
| Idelalisib | DRUG | Tablets administered orally |
| Placebo | DRUG | Capsules administered orally. |
Key Inclusion Criteria: * Documentation of relapsed or refractory CLL * Requiring treatment per modified International Workshop on CLL (IWCLL) 2008 criteria; adults without radiographically measureable disease (defined as ≥ 1 lesion \> 1.5 centimetres (cm) in diameter as assessed by computed tomogr...
Tirabrutinib is an investigational small molecule BTK inhibitor being developed by Gilead Sciences, Inc. (ticker GILD). It is being studied in oncology indications including chronic lymphocytic leukemia, non Hodgkin lymphoma, and relapsed or refractory B-cell malignancies, as well as in rheumatoid arthritis. It remains in clinical development and is not described as approved.
Tirabrutinib is being studied for chronic lymphocytic leukemia, non Hodgkin lymphoma, relapsed or refractory B-cell malignancies, and rheumatoid arthritis. These are investigational uses in clinical trials rather than approved indications. Development is led by Gilead Sciences, Inc. under ticker GILD.
Tirabrutinib targets Bruton tyrosine kinase, or BTK, and acts as a BTK inhibitor. BTK is an enzyme involved in B-cell receptor signaling, which is why the compound is being studied in B-cell cancers such as chronic lymphocytic leukemia and in rheumatoid arthritis.
Tirabrutinib is developed by Gilead Sciences, Inc., which trades under the ticker GILD. The company is the sponsor behind the clinical program evaluating the BTK inhibitor across B-cell malignancies and rheumatoid arthritis.
Tirabrutinib is in Phase 2 clinical development. The program includes Phase 2 studies in chronic lymphocytic leukemia and Phase 1 studies in relapsed or refractory B-cell malignancies and rheumatoid arthritis. It is investigational and is not described as FDA approved.
Tirabrutinib has been evaluated in completed trials including NCT02983617 and NCT02968563 in chronic lymphocytic leukemia, NCT02626026 in healthy volunteers and rheumatoid arthritis, and NCT02457559 in relapsed or refractory B-cell malignancies. These studies were conducted in Germany, the United States, France, and the United Kingdom.