Trial Outcomes & Findings for TAK-659 in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (NCT NCT03123393)

NCT ID: NCT03123393

Last Updated: 2023-02-08

Results Overview

ORR was defined as the percentage of participants with complete response (CR), or partial response (PR) as assessed by IRRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 49 participants
• Primary outcome timeframe: Up to 12 months
• Results posted on: 2023-02-08

Participant Flow

Participants took part in the study at 26 investigative sites in France, Great Britain, Italy, Spain, Canada, United States from 10 October 2017 to 17 December 2019. The study was terminated by the sponsor before the initiation of the stage 2 efficacy evaluation.

Participants with a diagnosis of relapsed or refractory diffuse large B-cell lymphoma who had at least 2 prior lines of chemotherapy were enrolled in Cohorts A and B. Cohort A received a single dose and Cohort B received ramp-up doses of TAK-659 in Stage 1 of the study.

Participant milestones

Measure	Cohort A: TAK-659 100 mg TAK-659 100 mg tablet, orally, once daily (QD), during each 28-days cycle (median exposure was 41 days).	Cohort B: TAK-659 Ramp-up Dosing TAK-659 60-100 mg tablet, orally, QD, dose based on safety and tolerability during each 28-days cycle (median exposure was 28 days).
Overall Study STARTED	24	25
Overall Study COMPLETED	3	2
Overall Study NOT COMPLETED	21	23

Reasons for withdrawal

Measure	Cohort A: TAK-659 100 mg TAK-659 100 mg tablet, orally, once daily (QD), during each 28-days cycle (median exposure was 41 days).	Cohort B: TAK-659 Ramp-up Dosing TAK-659 60-100 mg tablet, orally, QD, dose based on safety and tolerability during each 28-days cycle (median exposure was 28 days).
Overall Study Study Terminated by Sponsor	6	9
Overall Study Withdrawal by Subject	2	1
Overall Study Reason not Specified	13	13

Baseline Characteristics

TAK-659 in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Baseline characteristics by cohort

Measure	Cohort A: TAK-659 100 mg n=24 Participants TAK-659 100 mg tablet, orally, once daily (QD), during each 28-days cycle (median exposure was 41 days).	Cohort B: TAK-659 Ramp-up Dosing n=25 Participants TAK-659 60-100 mg tablet, orally, QD, dose based on safety and tolerability during each 28-days cycle (median exposure was 28 days).	Total n=49 Participants Total of all reporting groups
Age, Continuous	64.2 years STANDARD_DEVIATION 9.01 • n=5 Participants	64.6 years STANDARD_DEVIATION 11.37 • n=7 Participants	64.4 years STANDARD_DEVIATION 10.18 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	14 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	11 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	19 Participants n=7 Participants	40 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic and Latino	21 Participants n=5 Participants	13 Participants n=7 Participants	34 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment France	3 Participants n=5 Participants	11 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment United Kingdom	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Italy	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Spain	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Canada	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	10 Participants n=5 Participants	4 Participants n=7 Participants	14 Participants n=5 Participants
Height	172.8 cm STANDARD_DEVIATION 9.55 • n=5 Participants	167.5 cm STANDARD_DEVIATION 9.52 • n=7 Participants	170.1 cm STANDARD_DEVIATION 9.81 • n=5 Participants
Weight	92.88 kg STANDARD_DEVIATION 21.132 • n=5 Participants	72.81 kg STANDARD_DEVIATION 18.388 • n=7 Participants	82.64 kg STANDARD_DEVIATION 22.040 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 12 months

Population: As the study was terminated before the initiation of Stage 2, data was not collected for this outcome measure.

ORR was defined as the percentage of participants with complete response (CR), or partial response (PR) as assessed by IRRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

Population: As the study was terminated before the initiation of Stage 2, data was not collected for this outcome measure.

CR rate was defined as percentage of participants with complete response as assessed by IRC according to the modified 2007 IWG. CR was defined as disappearance of all evidence of disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

Population: As the study was terminated before the initiation of Stage 2, data was not collected for this outcome measure.

ORR was defined as the percentage of participants with CR or PR as assessed by IRRC according to the 2014 Lugano classification, IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

Population: As the study was terminated before the initiation of Stage 2, data was not collected for this outcome measure.

CR rate was defined as percentage of participants with complete response as assessed by IRC according to the 2014 Lugano classification, IWG criteria. CR was defined as disappearance of all evidence of disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

Population: As the study was terminated before the initiation of Stage 2, data was not collected for this outcome measure.

DOR was defined as the time from the date of first documentation of a CR/PR to the date of first documentation of tumor progression or progressive disease (PD) per IRRC assessment according to IWG criteria. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites. PD was defined as presence of any new lesion or increase by >=50% of previously involved sites from nadir.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

Population: As the study was terminated before the initiation of Stage 2, data was not collected for this outcome measure.

Duration of CR was defined as the time from the date of first documentation of a CR/PR to the date of first documentation of tumor progression or PD per IRRC assessment according to IWG criteria. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites. PD was defined as presence of any new lesion or increase by >=50% of previously involved sites from nadir.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

Population: As the study was terminated before the initiation of Stage 2, data was not collected for this outcome measure.

ORR was defined as the percentage of participants with CR or PR as assessed by IRRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

Population: As the study was terminated before the initiation of Stage 2, data was not collected for this outcome measure.

ORR was defined as the percentage of participants with CR or PR as assessed by IRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 18 months

Population: As the study was terminated before the initiation of Stage 2, data was not collected for this outcome measure.

PFS was defined as time from start of study treatment to first documentation of PD per IRC assessment or up to death due to any cause, whichever occurs first based on IWG criteria. PD was defined as presence of any new lesion or increase by >=50% of previously involved sites from nadir.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 24 months

Population: As the study was terminated before the initiation of Stage 2, data was not collected for this outcome measure.

OS was defined as the time from start of study treatment to date of death due to any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

Population: Data were not reported for this outcome measure because ORR was only assessed by the investigator on this study and not by IRRC as the study was terminated and the selection of dose for Stage 2 was not applicable.

ORR was defined as the percentage of participants with CR or PR as assessed by IRC. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Cycles 3, 6 and 9 (Up to 12 months) (Each cycle of 28 days)

Population: As the study was terminated before the initiation of Stage 2, data was not collected for this outcome measure.

ORR was defined as the percentage of participants with CR or PR as assessed by IRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

Outcome measures

Outcome data not reported

Adverse Events

Cohort A: TAK-659 100 mg

Serious events: 14 serious events

Other events: 24 other events

Deaths: 3 deaths

Cohort B: TAK-659 Ramp-up Dosing

Serious events: 13 serious events

Other events: 20 other events

Deaths: 3 deaths

Serious adverse events

Measure	Cohort A: TAK-659 100 mg n=24 participants at risk TAK-659 100 mg tablet, orally, once daily (QD), during each 28-days cycle (median exposure was 41 days).	Cohort B: TAK-659 Ramp-up Dosing n=25 participants at risk TAK-659 60-100 mg tablet, orally, QD, dose based on safety and tolerability during each 28-days cycle (median exposure was 28 days).
Blood and lymphatic system disorders Anaemia	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Bone marrow failure	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Lymphocytic infiltration	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pyrexia	12.5% 3/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Asthenia	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders General physical health deterioration	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Multiple organ dysfunction syndrome	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pain	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Pneumonia	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Sepsis	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Asymptomatic bacteriuria	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Candida sepsis	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Cellulitis	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Enterococcal bacteraemia	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Enterovirus infection	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Influenza	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Lung infection	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Pulmonary nocardiosis	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Rhinovirus infection	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Upper respiratory tract infection	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Urinary tract infection	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Animal bite	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Post procedural fever	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Aspartate aminotransferase increased	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Electrocardiogram QT prolonged	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Back pain	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Flank pain	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.0% 3/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal adenocarcinoma	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Encephalopathy	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Confusional state	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Measure	Cohort A: TAK-659 100 mg n=24 participants at risk TAK-659 100 mg tablet, orally, once daily (QD), during each 28-days cycle (median exposure was 41 days).	Cohort B: TAK-659 Ramp-up Dosing n=25 participants at risk TAK-659 60-100 mg tablet, orally, QD, dose based on safety and tolerability during each 28-days cycle (median exposure was 28 days).
General disorders Fatigue	25.0% 6/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	32.0% 8/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Oedema peripheral	29.2% 7/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Asthenia	12.5% 3/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Oedema	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Aspartate aminotransferase increased	37.5% 9/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 5/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Alanine aminotransferase increased	29.2% 7/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.0% 4/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Amylase increased	25.0% 6/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.0% 4/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood creatine phosphokinase increased	25.0% 6/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Lipase increased	16.7% 4/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.0% 3/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Gamma-glutamyltransferase increased	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.0% 4/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood alkaline phosphatase increased	16.7% 4/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood lactate dehydrogenase increased	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations C-reactive protein increased	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Neutrophil count decreased	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Platelet count decreased	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Anaemia	29.2% 7/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 5/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Neutropenia	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.0% 4/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Thrombocytopenia	12.5% 3/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Increased tendency to bruise	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Cough	37.5% 9/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.0% 3/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.7% 4/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.0% 3/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Sputum discoloured	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypophosphataemia	29.2% 7/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Decreased appetite	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Periorbital oedema	20.8% 5/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.0% 3/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Vision blurred	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Back pain	16.7% 4/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 3/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Myalgia	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Diarrhoea	16.7% 4/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal pain	16.7% 4/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Constipation	12.5% 3/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Nausea	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Dry mouth	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Vomiting	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal distension	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Oral candidiasis	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.0% 4/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Rash	20.8% 5/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Pruritus	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Headache	12.5% 3/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dizziness	12.5% 3/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Neuropathy peripheral	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Hypoaesthesia	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Contusion	12.5% 3/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hypertension	4.2% 1/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Acute kidney injury	8.3% 2/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Tachycardia	0.00% 0/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 2/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pyrexia	37.5% 9/24 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	40.0% 10/25 • From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER