Trial Outcomes & Findings for Study to Assess the Long-term Safety and Efficacy of Tirabrutinib in Adults With Relapsed/Refractory B-cell Malignancies (NCT NCT02457559)

Participants were enrolled at study sites in the United Kingdom and France. The first participant was screened on 10 September 2015. The last study visit occurred on 30 December 2020.

102 participants were screened. Participants must have been enrolled in parent study ONO-4059POE001 (NCT01659255) to be eligible to receive continued access to tirabrutinib in this rollover study. The dosing regimen was based on the prior dosing regimen from the parent study. As pre-specified in the protocol, the data from both the parent and rollover studies were analyzed together for participants in this rollover study.

Study to Assess the Long-term Safety and Efficacy of Tirabrutinib in Adults With Relapsed/Refractory B-cell Malignancies

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.

ORR was defined per Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for CLL and Cheson, 2007 criteria for NHL as percentage of participants who achieve partial response (PR) or complete response (CR) in either parent or roll-over study. CLL:CR: lymphocytes (Ly) \<4\*10\^9/L, no lymphadenopathy,normal spleen and liver size,absence of disease, absolute neutrophil count (ANC) \>1.5\*10\^9/L,platelets ≥100\*10\^9/L, hemoglobin (Hb) \>110 g/L,bone marrow at least normocellular for age; PR: ≥2 of these: ≥50% decrease in Ly, lymphadenopathy,size of liver and spleen, bone marrow infiltrates;and ≥1 of these: ANC \>1500/μL, platelets ≥100,000/µL, Hb \>11g/dL. NHL:CR: complete resolution of all disease-related radiological abnormalities; PR: ≥50% reduction in sum of products (SPD) of the longest diameters (LD) of all index lesions,no new lesions;no increase in size of liver or spleen;persistence of bone marrow involvement in participant who meets other criteria for CR.

DOR was defined per IWCLL 2008 criteria for CLL and Cheson, 2007 criteria for NHL as the interval from first documentation of CR or PR to the earlier of the first documentation of definitive disease progression as assessed by the investigator, or death from any cause in subjects who achieve a response. CLL:CR: Ly \<4\*10\^9/L, no lymphadenopathy, normal spleen and liver size, absence of disease, ANC \>1.5\*10\^9/L, platelets ≥100\*10\^9/L, Hb \>110 g/L, bone marrow at least normocellular for age; PR: ≥2 of these: ≥50% decrease in Ly, lymphadenopathy, size of liver and spleen, bone marrow infiltrates; and ≥1 of these: ANC \>1500/μL, platelets ≥100,000/µL, Hb \>11 g/dL. NHL:CR: complete resolution of all disease-related radiological abnormalities; PR: ≥50% reduction in SPD of the LD of all index lesions, no new lesions; no increase in size of liver or spleen; persistence of bone marrow involvement in participant who meets other criteria for CR.

PFS was defined per IWCLL 2008 criteria for CLL and Cheson 2007 criteria for NHL as the interval from date of the first dose of tirabrutinib on the parent study to the earlier of the first documentation of definitive disease progression as assessed by the investigator, or death from any cause. Progressive disease (PD) in CLL: Lymphadenopathy, or appearance of any new lesion/organomegaly, \> 50% increase in the size of the liver and/or spleen, Decrease in platelet count or hemoglobin attributable to CLL per IWCLL, Transformation to a more aggressive histology (eg, Richter syndrome). PD in NHL: Cheson, 2007: Appearance of new lesion or increase by \>50% of previously involved sites from nadir, Transformation to a more aggressive NHL histology.

OS is defined as the interval from date of the first dose of tirabrutinib on the parent study until death from any cause.