Trial Outcomes & Findings for Study to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib and Idelalisib With and Without Obinutuzumab in Adults With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) (NCT NCT02968563)

Last Updated: 2022-01-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

Week 25

Results posted on

2022-01-21

Participant Flow

Participants were enrolled at study sites in Germany. The first participant was screened on 13 December 2016. The last study visit occurred on 14 January 2021.

35 participants were screened. Randomization was discontinued after implementation of Protocol Amendment 3; all additional participants were enrolled to Arm: Tirabrutinib + Idelalisib + Obinutuzumab.

Participant milestones

Participant milestones
Measure	Tirabrutinib + Idelalisib Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.	Tirabrutinib + Idelalisib + Obinutuzumab Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally 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.
Overall Study STARTED	5	30
Overall Study COMPLETED	4	22
Overall Study NOT COMPLETED	1	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Tirabrutinib + Idelalisib Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.	Tirabrutinib + Idelalisib + Obinutuzumab Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally 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.
Overall Study Adverse Event	0	6
Overall Study Death	1	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Study to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib and Idelalisib With and Without Obinutuzumab in Adults With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tirabrutinib + Idelalisib n=5 Participants Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.	Tirabrutinib + Idelalisib + Obinutuzumab n=30 Participants Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally 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.	Total n=35 Participants Total of all reporting groups
Age, Continuous	62 years STANDARD_DEVIATION 4.7 • n=5 Participants	65 years STANDARD_DEVIATION 9.4 • n=7 Participants	65 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	10 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	20 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	5 Participants n=5 Participants	29 Participants n=7 Participants	34 Participants n=5 Participants
Race/Ethnicity, Customized Race · Not Permitted	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	5 Participants n=5 Participants	29 Participants n=7 Participants	34 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Permitted	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 25

Population: The Full Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug.

Outcome measures

Outcome measures
Measure	Tirabrutinib + Idelalisib n=5 Participants Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.	Tirabrutinib + Idelalisib + Obinutuzumab n=30 Participants Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally 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.
Rate of Complete Response/Complete Remission (CR), as Assessed by Investigator Using Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria at Week 25	0 percentage of participants Interval 0.0 to 45.1	6.7 percentage of participants Interval 1.2 to 19.5

SECONDARY outcome

Timeframe: Week 25

Population: Participants in the Full Analysis Set were analyzed.

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 \[hypocellular\] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with four-color-flow cytometry (FACS) and MRD negativity was defined as one CLL cell per 10,000 leukocytes \[0.01%\], ie,\<10\^-4 and participants were defined as MRD negative if their disease burden was below this threshold.

Outcome measures

Outcome measures
Measure	Tirabrutinib + Idelalisib n=5 Participants Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.	Tirabrutinib + Idelalisib + Obinutuzumab n=30 Participants Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally 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.
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 25	0 percentage of participants Interval 0.0 to 45.1	0 percentage of participants Interval 0.0 to 9.5

SECONDARY outcome

Timeframe: Week 25

Population: Participants in the Full Analysis Set were analyzed.

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 \[hypocellular\] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with FACS and MRD negativity was defined as one CLL cell per 10,000 leukocytes \[0.01%\], ie,\<10\^-4 and participants were defined as MRD negative if their disease burden was below this threshold.

Outcome measures

Outcome measures
Measure	Tirabrutinib + Idelalisib n=5 Participants Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.	Tirabrutinib + Idelalisib + Obinutuzumab n=30 Participants Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally 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.
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 25	0 percentage of participants Interval 0.0 to 45.1	0 percentage of participants Interval 0.0 to 9.5

SECONDARY outcome

Timeframe: Week 25

Population: Participants in the Full Analysis Set were analyzed.

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 \>11 g/dL or ≥ 50% increase from Baseline. PR-L: meeting PR criteria; however, a lymphocytosis related to treatment may be present. nPR: All criteria for a CR/CRi were fulfilled, but the bone marrow showed lymphoid nodules.

Outcome measures

Outcome measures
Measure	Tirabrutinib + Idelalisib n=5 Participants Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.	Tirabrutinib + Idelalisib + Obinutuzumab n=30 Participants Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally 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.
Overall Response Rate (ORR), as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25	60.0 percentage of participants Interval 18.9 to 92.4	93.3 percentage of participants Interval 80.5 to 98.8

SECONDARY outcome

Timeframe: First dose date up to the last dose date (maximum: 105 weeks) plus 30 days

Population: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug.

Treatment-emergent AEs are 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 * Any AEs 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.

Outcome measures

Outcome measures
Measure	Tirabrutinib + Idelalisib n=5 Participants Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.	Tirabrutinib + Idelalisib + Obinutuzumab n=30 Participants Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally 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.
Percentage of Participants Experiencing Any Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs) Any Treatment-Emergent AEs	100 percentage of participants	100 percentage of participants
Percentage of Participants Experiencing Any Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs) Treatment-Emergent SAEs	60.0 percentage of participants	46.7 percentage of participants

Adverse Events

Tirabrutinib + Idelalisib

Serious events: 3 serious events

Other events: 5 other events

Deaths: 1 deaths

Tirabrutinib + Idelalisib + Obinutuzumab

Serious events: 14 serious events

Other events: 29 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER

Measure	Tirabrutinib + Idelalisib n=5 participants at risk Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.	Tirabrutinib + Idelalisib + Obinutuzumab n=30 participants at risk Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally 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 administered intravenously over 21 weeks.
Cardiac disorders Cardiac failure acute	20.0% 1/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	0.00% 0/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Cardiac disorders Coronary artery stenosis	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Gastrointestinal disorders Colitis	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Gastrointestinal disorders Stomatitis	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Infections and infestations Atypical pneumonia	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Infections and infestations Cystitis	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Infections and infestations Influenza	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Infections and infestations Large intestine infection	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Infections and infestations Pneumonia	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Investigations Hepatic enzyme increased	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Investigations Investigation	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Investigations Neutrophil count decreased	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Metabolism and nutrition disorders Tumour lysis syndrome	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Nervous system disorders Cerebral infarction	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Renal and urinary disorders Nephrolithiasis	20.0% 1/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	0.00% 0/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Renal and urinary disorders Ureterolithiasis	20.0% 1/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	0.00% 0/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	3.3% 1/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Skin and subcutaneous tissue disorders Dermatitis allergic	20.0% 1/5 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.	0.00% 0/30 • Adverse Events: First dose date up to last dose date (maximum: 105 weeks) plus 30 days; All-Cause Mortality: Enrollment up to 31 months Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug. All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.