Trial Outcomes & Findings for A Study of JNJ-26866138 (Bortezomib) in Untreated Multiple Myeloma Patients Who Are Not Candidates for Hematopoietic Stem Cell Transplant (HSCT) (NCT NCT00985959)

Last Updated: 2013-12-02

Results Overview

Dose limiting toxicity defined as an adverse event or adverse drug reaction experienced by the participants during 6 weeks of treatment Cycle 1

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

101 participants

Primary outcome timeframe

6 weeks

Results posted on

2013-12-02

Participant Flow

Total 101 participants (Phase I: 18 and Phase II: 83) were enrolled at multiple sites in Japan.

18 participants were enrolled and treated in Phase I. Total 89 participants were enrolled in Phase II (including 6 participants receiving 1.3 mg/m2 in the Phase I part). Of the 89 participants, 87 were received at least 1 dose of study medication. 2 participants were not treated.

Participant milestones

Participant milestones
Measure	Phase I - JNJ-26866138 0.7 mg/m2 Group JNJ-26866138 0.7 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.0 mg/m2 Group JNJ-26866138 1.0 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I and II - JNJ-26866138 1.3 mg/m2 Group Phase I: JNJ-26866138 1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles. Phase II: JNJ-26866138 1.3 mg/m2 on Days 1, 8, 22 and 29 of 6-week cycle for 5-9 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles
Overall Study STARTED	6	6	87
Overall Study COMPLETED	3	3	28
Overall Study NOT COMPLETED	3	3	59

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I - JNJ-26866138 0.7 mg/m2 Group JNJ-26866138 0.7 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.0 mg/m2 Group JNJ-26866138 1.0 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I and II - JNJ-26866138 1.3 mg/m2 Group Phase I: JNJ-26866138 1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles. Phase II: JNJ-26866138 1.3 mg/m2 on Days 1, 8, 22 and 29 of 6-week cycle for 5-9 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles
Overall Study Adverse Event	0	0	19
Overall Study Withdrawal by Subject	0	0	8
Overall Study Progressive disease	1	2	8
Overall Study Unrecovered toxicity	0	0	7
Overall Study Pneumonitis or pulmonary fibrosis	2	0	2
Overall Study Complete response observed over 2 cycles	0	1	4
Overall Study Other	0	0	11

Baseline Characteristics

A Study of JNJ-26866138 (Bortezomib) in Untreated Multiple Myeloma Patients Who Are Not Candidates for Hematopoietic Stem Cell Transplant (HSCT)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I - JNJ-26866138 0.7 mg/m2 Group n=6 Participants JNJ-26866138 0.7 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.0 mg/m2 Group n=6 Participants JNJ-26866138 1.0 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I and II - JNJ-26866138 1.3 mg/m2 Group n=87 Participants Phase I: JNJ-26866138 1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles. Phase II: JNJ-26866138 1.3 mg/m2 on Days 1, 8, 22 and 29 of 6-week cycle for 5-9 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles	Total n=99 Participants Total of all reporting groups
Age Continuous	72.7 Years STANDARD_DEVIATION 9.2 • n=5 Participants	68.5 Years STANDARD_DEVIATION 6.47 • n=7 Participants	70.9 Years STANDARD_DEVIATION 5.68 • n=5 Participants	70.9 Years STANDARD_DEVIATION 5.94 • n=4 Participants
Age, Customized <65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants
Age, Customized >= 65 and <= 74 years	2 Participants n=5 Participants	5 Participants n=7 Participants	60 Participants n=5 Participants	67 Participants n=4 Participants
Age, Customized >=75 years	3 Participants n=5 Participants	0 Participants n=7 Participants	24 Participants n=5 Participants	27 Participants n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	51 Participants n=5 Participants	57 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	36 Participants n=5 Participants	42 Participants n=4 Participants

PRIMARY outcome

Timeframe: 6 weeks

Population: Dose Limiting Toxicity set, Which includes all 18 participants in the Phase I

Dose limiting toxicity defined as an adverse event or adverse drug reaction experienced by the participants during 6 weeks of treatment Cycle 1

Outcome measures

Outcome measures
Measure	Phase I - JNJ-26866138 0.7 mg/m2 Group n=6 Participants JNJ-26866138 0.7 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.0 mg/m2 Group n=6 Participants JNJ-26866138 1.0 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.3 mg/m2 Group n=6 Participants JNJ-26866138 1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase II - JNJ-26866138 1.3 mg/m2 Group JNJ-26866138 1.3 mg/m2 on Days 1, 8, 22 and 29 of 6-week cycle for 5-9 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles	Total Participants from both Phase I and Phase II
Number of Participants With Dose Limiting Toxicity During the Phase I (Cycle 1)	0 Participants	0 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: 54 weeks

Population: Full analysis set: All participants who received at least one dose of the study medication.

Response is evaluated as per the criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation (Blade et al. 1998). CR: disappearance of the original monoclonal protein from the blood and urine and \<5% plasma cells in the bone marrow on at least 2 determinations for a minimum of 6 weeks; no increase in the size or number of lytic bone lesions; disappearance of soft tissue plasmacytomas for at least 6 weeks. PR: ≥50% reduction in the level of serum monoclonal protein for at least 2 determinations 6 weeks apart; If present, reduction in 24-hour urinary light chain excretion by either ≥90% or to \<200 mg for at least 2 determinations 6 weeks apart; ≥50% reduction in the size of soft tissue plasmacytomas for at least 6 weeks; no increase in size or number of lytic bone lesions

Outcome measures

Outcome measures
Measure	Phase I - JNJ-26866138 0.7 mg/m2 Group n=6 Participants JNJ-26866138 0.7 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.0 mg/m2 Group n=6 Participants JNJ-26866138 1.0 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.3 mg/m2 Group n=5 Participants JNJ-26866138 1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase II - JNJ-26866138 1.3 mg/m2 Group n=86 Participants JNJ-26866138 1.3 mg/m2 on Days 1, 8, 22 and 29 of 6-week cycle for 5-9 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles	Total n=98 Participants Participants from both Phase I and Phase II
Number of Participants With Overall Response (Complete Response [CR] + Partial Response [PR]) - Phase I and II	6 Participants Interval 54.1 to 100.0	5 Participants Interval 35.9 to 99.6	4 Participants Interval 28.4 to 99.5	60 Participants Interval 58.9 to 79.2	71 Participants

SECONDARY outcome

Timeframe: Day 25 of Cycle 1

Population: Pharmacokinetics-evaluable population: 16 participants were included in pharmacokinetics-evaluable population

Cmax of bortezomib following intravenous administration of JNJ-26866138 at dose of 0.7, 1.0, and 1.3 mg/m2 on Cycle 1/Day 25 (JNJ-26866138 alone)

Outcome measures

Outcome measures
Measure	Phase I - JNJ-26866138 0.7 mg/m2 Group n=6 Participants JNJ-26866138 0.7 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.0 mg/m2 Group n=6 Participants JNJ-26866138 1.0 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.3 mg/m2 Group n=4 Participants JNJ-26866138 1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase II - JNJ-26866138 1.3 mg/m2 Group JNJ-26866138 1.3 mg/m2 on Days 1, 8, 22 and 29 of 6-week cycle for 5-9 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles	Total Participants from both Phase I and Phase II
Maximum Observed Plasma Concentration (Cmax) of Bortezomib (JNJ-26866138 Alone) - Phase I	45.43 ng/mL Standard Deviation 10.087	59.42 ng/mL Standard Deviation 18.89	120.3 ng/mL Standard Deviation 24.527	—	—

SECONDARY outcome

Timeframe: Day 4 of Cycle 2

Population: Pharmacokinetics-evaluable population: 14 participants were included in pharmacokinetics-evaluable population during Cycle 2

Cmax of bortezomib following intravenous administration of JNJ-26866138 at dose of 0.7, 1.0, and 1.3 mg/m2 on Cycle 2/Day 4 (combination with melphalan and prednisolone)

Outcome measures

Outcome measures
Measure	Phase I - JNJ-26866138 0.7 mg/m2 Group n=6 Participants JNJ-26866138 0.7 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.0 mg/m2 Group n=5 Participants JNJ-26866138 1.0 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.3 mg/m2 Group n=3 Participants JNJ-26866138 1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase II - JNJ-26866138 1.3 mg/m2 Group JNJ-26866138 1.3 mg/m2 on Days 1, 8, 22 and 29 of 6-week cycle for 5-9 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles	Total Participants from both Phase I and Phase II
Maximum Observed Plasma Concentration (Cmax) of Bortezomib (JNJ-26866138 in Combination With Melphalan and Prednisolone) - Phase I	34.40 ng/mL Standard Deviation 5.7986	69.50 ng/mL Standard Deviation 19.455	88.87 ng/mL Standard Deviation 19.568	—	—

SECONDARY outcome

Timeframe: Day 4 of Cycle 2

Population: Pharmacokinetics-evaluable population: 14 participants were included in pharmacokinetics-evaluable population during Cycle 2

Cmax of melphalan at dose of 9 mg/m2 on Cycle 2/Day 4

Outcome measures

Outcome measures
Measure	Phase I - JNJ-26866138 0.7 mg/m2 Group n=14 Participants JNJ-26866138 0.7 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.0 mg/m2 Group JNJ-26866138 1.0 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.3 mg/m2 Group JNJ-26866138 1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase II - JNJ-26866138 1.3 mg/m2 Group JNJ-26866138 1.3 mg/m2 on Days 1, 8, 22 and 29 of 6-week cycle for 5-9 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles	Total Participants from both Phase I and Phase II
Maximum Observed Plasma Concentration (Cmax) of Melphalan - Phase I	100.2 ng/mL Standard Deviation 49.515	—	—	—	—

SECONDARY outcome

Timeframe: Day 4 of Cycle 2

Population: Pharmacokinetics-evaluable population: 14 participants were included in pharmacokinetics-evaluable population during Cycle 2

Cmax of Prednisolone at dose of 60 mg/m2 on Cycle 2/Day 4

Outcome measures

Outcome measures
Measure	Phase I - JNJ-26866138 0.7 mg/m2 Group n=14 Participants JNJ-26866138 0.7 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.0 mg/m2 Group JNJ-26866138 1.0 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.3 mg/m2 Group JNJ-26866138 1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase II - JNJ-26866138 1.3 mg/m2 Group JNJ-26866138 1.3 mg/m2 on Days 1, 8, 22 and 29 of 6-week cycle for 5-9 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles	Total Participants from both Phase I and Phase II
Maximum Observed Plasma Concentration (Cmax) of Prednisolone - Phase I	1131 ng/mL Standard Deviation 223.92	—	—	—	—

SECONDARY outcome

Timeframe: up to 54 weeks

Population: Full analysis set: All participants who received at least one dose of the study medication.

Time to first response is the duartion of time required to achieve first response to treatment

Outcome measures

Outcome measures
Measure	Phase I - JNJ-26866138 0.7 mg/m2 Group n=86 Participants JNJ-26866138 0.7 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.0 mg/m2 Group JNJ-26866138 1.0 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.3 mg/m2 Group JNJ-26866138 1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase II - JNJ-26866138 1.3 mg/m2 Group JNJ-26866138 1.3 mg/m2 on Days 1, 8, 22 and 29 of 6-week cycle for 5-9 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles	Total Participants from both Phase I and Phase II
Median Time to First Response - Phase II	51 Days Interval 43.0 to 82.0	—	—	—	—

Adverse Events

Phase I - JNJ-26866138 0.7 mg/m2 Group

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase I - JNJ-26866138 1.0 mg/m2 Group

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase I - JNJ-26866138 1.3 mg/m2 Group

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase II - JNJ-26866138 1.3 mg/m2 Group

Serious events: 29 serious events

Other events: 87 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Director

Janssen Pharm KK Japan

Phone: +81-3-4411-5801

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Phase I - JNJ-26866138 0.7 mg/m2 Group n=6 participants at risk JNJ-26866138 0.7 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.0 mg/m2 Group n=6 participants at risk JNJ-26866138 1.0 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase I - JNJ-26866138 1.3 mg/m2 Group n=6 participants at risk JNJ-26866138 1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles	Phase II - JNJ-26866138 1.3 mg/m2 Group n=87 participants at risk JNJ-26866138 1.3 mg/m2 on Days 1, 8, 22 and 29 of 6-week cycle for 5-9 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles
Infections and infestations Bronchopulmonary aspergillosis	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Infections and infestations Herpes zoster	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Infections and infestations Nasopharyngitis	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Infections and infestations Pneumonia	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Infections and infestations Pneumonia pneumococcal	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Infections and infestations Septic shock	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Infections and infestations Upper respiratory tract infection	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Infections and infestations Herpes zoster dissemin	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Infections and infestations Enterocolitis bacterial	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Blood and lymphatic system disorders Anaemia	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Metabolism and nutrition disorders Tumour lysis syndrome	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	2.3% 2/87 • Number of events 2 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Metabolism and nutrition disorders Hypophagia	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Psychiatric disorders Depression	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Nervous system disorders Neuropathy peripheral	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Eye disorders Cataract	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Eye disorders Glaucoma	16.7% 1/6 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/87 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Cardiac disorders Prinzmetal angina	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	2.3% 2/87 • Number of events 2 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	16.7% 1/6 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/87 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Gastrointestinal disorders Diarrhoea	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	2.3% 2/87 • Number of events 2 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Gastrointestinal disorders Enterocolitis	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	2.3% 2/87 • Number of events 2 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Gastrointestinal disorders Constipation	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Gastrointestinal disorders Ileus	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Gastrointestinal disorders Nausea	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Skin and subcutaneous tissue disorders Rash	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	16.7% 1/6 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	2.3% 2/87 • Number of events 2 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Renal and urinary disorders Renal failure	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	16.7% 1/6 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/87 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Renal and urinary disorders Renal failure acute	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Renal and urinary disorders Renal impairment	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
General disorders Asthenia	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
General disorders Pyrexia	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	16.7% 1/6 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/87 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	0.00% 0/6 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.	1.1% 1/87 • Number of events 1 • 54 weeks 87 participants who received at least 1 dose of study medication were evaluated for safety.