Trial Outcomes & Findings for KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL) (NCT NCT01626664)

Last Updated: 2024-04-25

Results Overview

Overall Response Rate was determined based on the response in all compartments (lymph nodes, extranodal masses, spleen/liver, skin, peripheral blood, and bone marrow), referencing Tsukasaki, 2009 as follows: Complete Response (CR) = All compartments involved with disease must be CR; Uncertified Complete Response (CRu) = \> 75% decrease in lymph nodes and/or extranodal disease with all other compartments involved with disease CR; Partial Response (PR) = If any compartment is CR/PR and all other compartments involved with disease are at least SD; Stable Disease (SD) = All compartments involved with disease are SD; Progressive Disease (PD) = PD in any compartment. Lymph node and extranodal masses response ≥50% decrease by CT, skin response ≥50% decrease in mSWAT score; blood response ≥50% decrease in malignant cells by flow cytometry; normal bone marrow if abnormal at baseline. PD equals New or ≥50% increase in any compartment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

71 participants

Primary outcome timeframe

every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first

Results posted on

2024-04-25

Participant Flow

Participant milestones

Participant milestones
Measure	KW-0761 anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression	Investigator's Choice Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP Pralatrexate: 30 mg/m2 weekly for 3 weeks followed by 1 week of no therapy until progression gemcitabine plus oxaliplatin: gemcitabine 1000 mg/m2, followed by oxaliplatin 100 mg/m2 every 2 weeks until progression DHAP: dexamethasone 40 mg on Day 1-4, cisplatin 100 mg/m2 on Day 1 followed by 2 doses of cytarabine 2000 mg/m2 every 4 weeks until progression	IC Original Then Crossover to KW-0761 Subjects who were randomized to the Investigator's Choice regimen could be crossed over to receive mogamulizumab upon disease progression and with permission from the Medical Monitor.
Randomization Period STARTED	47	24	0
Randomization Period COMPLETED	47	24	0
Randomization Period NOT COMPLETED	0	0	0
Crossover Period STARTED	0	0	18
Crossover Period COMPLETED	0	0	18
Crossover Period NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	KW-0761 n=47 Participants anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression	Investigator's Choice n=24 Participants Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP Pralatrexate: 30 mg/m2 weekly for 3 weeks followed by 1 week of no therapy until progression gemcitabine plus oxaliplatin: gemcitabine 1000 mg/m2, followed by oxaliplatin 100 mg/m2 every 2 weeks until progression DHAP: dexamethasone 40 mg on Day 1-4, cisplatin 100 mg/m2 on Day 1 followed by 2 doses of cytarabine 2000 mg/m2 every 4 weeks until progression	Total n=71 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	35 Participants n=5 Participants	22 Participants n=7 Participants	57 Participants n=5 Participants
Age, Categorical >=65 years	12 Participants n=5 Participants	2 Participants n=7 Participants	14 Participants n=5 Participants
Age, Continuous	55 years n=5 Participants	49 years n=7 Participants	53 years n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	14 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	10 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants	14 Participants n=7 Participants	45 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	32 Participants n=5 Participants	15 Participants n=7 Participants	47 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Not Applicable	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants	14 participants n=7 Participants	39 participants n=5 Participants
Region of Enrollment Brazil	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United Kingdom	9 participants n=5 Participants	4 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment France	6 participants n=5 Participants	3 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Peru	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants

PRIMARY outcome

Timeframe: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first

Outcome measures

Outcome measures
Measure	KW-0761 n=47 Participants anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression	Investigator's Choice n=24 Participants Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP Pralatrexate: 30 mg/m2 weekly for 3 weeks followed by 1 week of no therapy until progression gemcitabine plus oxaliplatin: gemcitabine 1000 mg/m2, followed by oxaliplatin 100 mg/m2 every 2 weeks until progression DHAP: dexamethasone 40 mg on Day 1-4, cisplatin 100 mg/m2 on Day 1 followed by 2 doses of cytarabine 2000 mg/m2 every 4 weeks until progression
Overall Response Rate Complete Response	2 participants	0 participants
Overall Response Rate Uncertified Complete Response	0 participants	0 participants
Overall Response Rate Partial Response	11 participants	2 participants
Overall Response Rate Stable Disease	0 participants	4 participants
Overall Response Rate Relapsed Disease or Progressive Disease	16 participants	13 participants
Overall Response Rate Not Assessable	18 participants	5 participants
Overall Response Rate Overall Response Rate (Confirmed and Unconfirmed)	13 participants	2 participants
Overall Response Rate Overall Response Rate Confirmed	5 participants	0 participants

SECONDARY outcome

Timeframe: From date of randomization until the date of first documented progression, start of alternative therapy, or date of death from any cause, whichever came first, up to 36 months

Progression-free survival was defined as the time from the first date of treatment until the date that PD or death was first reported. Disease progression included PD in any compartment per ATL response criteria, clinical progression at the end of the randomized treatment, or disease progression reported during the follow-up period. The date of PD was the earliest date at which disease progression could be declared.

Outcome measures

Outcome measures
Measure	KW-0761 n=47 Participants anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression	Investigator's Choice n=24 Participants Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP Pralatrexate: 30 mg/m2 weekly for 3 weeks followed by 1 week of no therapy until progression gemcitabine plus oxaliplatin: gemcitabine 1000 mg/m2, followed by oxaliplatin 100 mg/m2 every 2 weeks until progression DHAP: dexamethasone 40 mg on Day 1-4, cisplatin 100 mg/m2 on Day 1 followed by 2 doses of cytarabine 2000 mg/m2 every 4 weeks until progression
Progression Free Survival PFS Subjects (%) Alive for at Least: 1 Month	47.5 percentage of subjects Interval 31.6 to 61.9	44.1 percentage of subjects Interval 22.8 to 63.4
Progression Free Survival PFS Subjects (%) Alive for at Least: 2 Months	29.8 percentage of subjects Interval 16.6 to 44.2	33.0 percentage of subjects Interval 14.2 to 53.3
Progression Free Survival PFS Subjects (%) Alive for at Least: 3 Months	24.4 percentage of subjects Interval 12.4 to 38.5	26.4 percentage of subjects Interval 9.4 to 47.3
Progression Free Survival PFS Subjects (%) Alive for at Least: 4 Months	18.3 percentage of subjects Interval 7.9 to 32.1	13.2 percentage of subjects Interval 2.4 to 33.5
Progression Free Survival PFS Subjects (%) Alive for at Least: 5 Months	18.3 percentage of subjects Interval 7.9 to 32.1	0 percentage of subjects Interval 0.0 to 0.0
Progression Free Survival PFS Subjects (%) Alive for at Least: 6 Months	12.2 percentage of subjects Interval 4.0 to 25.1	0 percentage of subjects Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: up to 36 months

The estimates and summary statistics for OS were calculated based on Kaplan-Meier method, and the median OS was 4.9 months for subjects randomized to the mogamulizumab group versus 6.87 months for subjects randomized to the Investigator's Choice group.

Outcome measures

Outcome measures
Measure	KW-0761 n=47 Participants anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression	Investigator's Choice n=24 Participants Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP Pralatrexate: 30 mg/m2 weekly for 3 weeks followed by 1 week of no therapy until progression gemcitabine plus oxaliplatin: gemcitabine 1000 mg/m2, followed by oxaliplatin 100 mg/m2 every 2 weeks until progression DHAP: dexamethasone 40 mg on Day 1-4, cisplatin 100 mg/m2 on Day 1 followed by 2 doses of cytarabine 2000 mg/m2 every 4 weeks until progression
Overall Survival Subjects (%) Alive for at Least: 5 Months	49.5 percentage of subjects Interval 33.9 to 63.3	54.2 percentage of subjects Interval 32.7 to 71.4
Overall Survival Subjects (%) Alive for at Least: 6 Months	44.3 percentage of subjects Interval 29.1 to 58.5	54.2 percentage of subjects Interval 32.7 to 71.4
Overall Survival Subjects (%) Alive for at Least: 1 Month	87.0 percentage of subjects Interval 73.2 to 93.9	91.7 percentage of subjects Interval 70.6 to 97.8
Overall Survival Subjects (%) Alive for at Least: 2 Months	75.6 percentage of subjects Interval 60.3 to 85.7	79.2 percentage of subjects Interval 57.0 to 90.8
Overall Survival Subjects (%) Alive for at Least: 3 Months	59.1 percentage of subjects Interval 43.1 to 72.0	70.8 percentage of subjects Interval 48.4 to 84.9
Overall Survival Subjects (%) Alive for at Least: 4 Months	54.3 percentage of subjects Interval 38.5 to 67.7	66.7 percentage of subjects Interval 44.3 to 81.7

SECONDARY outcome

Timeframe: From date of randomization until the date of first documented progression, up to 36 months

Population: All participants in Intention-to-Treat who had both the values at baseline and last observation

The FACT-Lym consists of a 27-item general core questionnaire (i.e., Functional Assessment of Cancer Therapy - General \[FACT-G\]) and a 15-item disease-specific questionnaire (Lymphoma Subscale). The FACT-G includes 4 domains: physical well-being, social/family well-being, emotional well-being, and functional well-being. The total FACT-Lym score (0-168) was obtained by summing individual subscale scores. Higher scores for the scales indicate better quality of life. Change was calculated as the value at the last observation minus the value at baseline.

Outcome measures

Outcome measures
Measure	KW-0761 n=41 Participants anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression	Investigator's Choice n=24 Participants Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP Pralatrexate: 30 mg/m2 weekly for 3 weeks followed by 1 week of no therapy until progression gemcitabine plus oxaliplatin: gemcitabine 1000 mg/m2, followed by oxaliplatin 100 mg/m2 every 2 weeks until progression DHAP: dexamethasone 40 mg on Day 1-4, cisplatin 100 mg/m2 on Day 1 followed by 2 doses of cytarabine 2000 mg/m2 every 4 weeks until progression
Change in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score Baseline	110.1 Units on a scale Standard Deviation 22.15	106.8 Units on a scale Standard Deviation 25.84
Change in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score Last Observation Change from Baseline	-12.1 Units on a scale Standard Deviation 25.60	-14.9 Units on a scale Standard Deviation 25.56

Adverse Events

KW-0761

Serious events: 26 serious events

Other events: 45 other events

Deaths: 10 deaths

Investigator's Choice

Serious events: 10 serious events

Other events: 24 other events

Deaths: 1 deaths

IC Original Then Crossover to KW-0761

Serious events: 9 serious events

Other events: 17 other events

Deaths: 12 deaths

Serious adverse events

Other adverse events

Additional Information

Fiona Herr, Associate Director, Medical Communications

Kyowa Kirin Inc

Phone: 1 (908) 234-1096

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	KW-0761 n=47 participants at risk anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression	Investigator's Choice n=24 participants at risk Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP Pralatrexate: 30 mg/m2 weekly for 3 weeks followed by 1 week of no therapy until progression gemcitabine plus oxaliplatin: gemcitabine 1000 mg/m2, followed by oxaliplatin 100 mg/m2 every 2 weeks until progression DHAP: dexamethasone 40 mg on Day 1-4, cisplatin 100 mg/m2 on Day 1 followed by 2 doses of cytarabine 2000 mg/m2 every 4 weeks until progression	IC Original Then Crossover to KW-0761 n=18 participants at risk Subjects who were randomized to the Investigator's Choice regimen could be crossed over to receive mogamulizumab upon disease progression and with permission from the Medical Monitor.
Blood and lymphatic system disorders Anaemia	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Blood and lymphatic system disorders Leukocytosis	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	4.2% 1/24 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	8.3% 2/24 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Cardiac disorders Acute Coronary Syndrome	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Cardiac disorders Acute Myocardial Infarction	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Cardiac disorders Atrial Fibrillation	4.3% 2/47 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Cardiac disorders Myocarditis	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	4.2% 1/24 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Abdominal Distension	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Abdominal Pain	2.1% 1/47 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	4.2% 1/24 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Constipation	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Haematemsis	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Ileitis	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	4.2% 1/24 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Nausea	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	4.2% 1/24 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Vomiting	4.3% 2/47 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	4.2% 1/24 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Asthenia	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Disease Progression	4.3% 2/47 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Fatigue	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Multi-Organ Failure	4.3% 2/47 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Pyrexia	4.3% 2/47 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Immune system disorders Anaphylactic Reaction	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Catheter Site Infection	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Cellulitis	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	4.2% 1/24 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Clostridial Infection	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Cytomegalovirus Infection	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Empyema	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Infective Thrombosis	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Lower Respiratory Tract Infection	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Oropharyngeal Candidiasis	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Pneumocystis Jiroveci Pneumonia	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Pneumonia	6.4% 3/47 • Number of events 4 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Post Procedural Sepsis	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Sepsis	4.3% 2/47 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Septic Shock	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Urosepsis	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Injury, poisoning and procedural complications Infusion Related Reaction	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Investigations Alanine Aminotransferase Increased	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Investigations Amylase Increased	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	4.2% 1/24 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Investigations Aspartate Aminotransferase Increased	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	4.2% 1/24 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Investigations Bilirubin Conjugated Increased	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Investigations Blood Alkaline Phosphatase Increased	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall

Other adverse events
Measure	KW-0761 n=47 participants at risk anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression	Investigator's Choice n=24 participants at risk Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP Pralatrexate: 30 mg/m2 weekly for 3 weeks followed by 1 week of no therapy until progression gemcitabine plus oxaliplatin: gemcitabine 1000 mg/m2, followed by oxaliplatin 100 mg/m2 every 2 weeks until progression DHAP: dexamethasone 40 mg on Day 1-4, cisplatin 100 mg/m2 on Day 1 followed by 2 doses of cytarabine 2000 mg/m2 every 4 weeks until progression	IC Original Then Crossover to KW-0761 n=18 participants at risk Subjects who were randomized to the Investigator's Choice regimen could be crossed over to receive mogamulizumab upon disease progression and with permission from the Medical Monitor.
Psychiatric disorders Anxiety	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	8.3% 2/24 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	16.7% 3/18 • Number of events 3 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Psychiatric disorders Confusional State	6.4% 3/47 • Number of events 3 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	11.1% 2/18 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Psychiatric disorders Hallucination	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Psychiatric disorders Insomnia	10.6% 5/47 • Number of events 5 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	8.3% 2/24 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Renal and urinary disorders Proteinuria	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Renal and urinary disorders Renal Failure Acute	6.4% 3/47 • Number of events 3 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Renal and urinary disorders Renail Impairment	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Reproductive system and breast disorders Sexual Dysfunction	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Respiratory, thoracic and mediastinal disorders Acute Pulmonary Oedema	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Blood and lymphatic system disorders Anaemia	21.3% 10/47 • Number of events 13 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	12.5% 3/24 • Number of events 10 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	33.3% 6/18 • Number of events 11 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Blood and lymphatic system disorders Leukocytosis	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	11.1% 2/18 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Blood and lymphatic system disorders Leukopenia	6.4% 3/47 • Number of events 3 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	4.2% 1/24 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Blood and lymphatic system disorders Neutropenia	8.5% 4/47 • Number of events 10 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	16.7% 4/24 • Number of events 8 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	11.1% 2/18 • Number of events 3 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Blood and lymphatic system disorders Pancytopenia	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Blood and lymphatic system disorders Thrombocytopenia	12.8% 6/47 • Number of events 8 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	12.5% 3/24 • Number of events 5 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	11.1% 2/18 • Number of events 3 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Cardiac disorders Bradycardia	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Cardiac disorders Tachycardia	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	11.1% 2/18 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Endocrine disorders Hypothyroidism	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Abdominal Distension	2.1% 1/47 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	8.3% 2/24 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	11.1% 2/18 • Number of events 3 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Abdominal Pain	14.9% 7/47 • Number of events 7 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	8.3% 2/24 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	11.1% 2/18 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Constipation	12.8% 6/47 • Number of events 7 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	20.8% 5/24 • Number of events 5 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Diarrhoea	6.4% 3/47 • Number of events 3 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	29.2% 7/24 • Number of events 9 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	11.1% 2/18 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Diarrhoea Haemorrhagic	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Dry Mouth	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Gastrooesophageal Reflux Disease	6.4% 3/47 • Number of events 3 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	4.2% 1/24 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Haematochezia	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Nausea	12.8% 6/47 • Number of events 7 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	37.5% 9/24 • Number of events 11 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Obstruction Gastric	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Gastrointestinal disorders Vomiting	8.5% 4/47 • Number of events 6 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	29.2% 7/24 • Number of events 7 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Asthenia	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	16.7% 3/18 • Number of events 3 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Chest Pain	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Chills	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	11.1% 2/18 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Fatigue	10.6% 5/47 • Number of events 8 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	16.7% 4/24 • Number of events 4 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Gait Disturbance	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	11.1% 2/18 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Malaise	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	12.5% 3/24 • Number of events 3 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Mucosal Inflammation	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	8.3% 2/24 • Number of events 2 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Oedema Peripheral	17.0% 8/47 • Number of events 8 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	16.7% 4/24 • Number of events 4 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	16.7% 3/18 • Number of events 3 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Pain	6.4% 3/47 • Number of events 3 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
General disorders Pyrexia	8.5% 4/47 • Number of events 4 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	25.0% 6/24 • Number of events 18 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	16.7% 3/18 • Number of events 3 • From pre-treatment visit until 90 days after the last dose, approximately three months overall
Infections and infestations Aspergillosis	0.00% 0/47 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	0.00% 0/24 • From pre-treatment visit until 90 days after the last dose, approximately three months overall	5.6% 1/18 • Number of events 1 • From pre-treatment visit until 90 days after the last dose, approximately three months overall