Trial Outcomes & Findings for A Phase 3 Trial of Brentuximab Vedotin(SGN-35) Versus Physician's Choice (Methotrexate or Bexarotene) in Participants With CD30-Positive Cutaneous T-Cell Lymphoma (ALCANZA Study) (NCT NCT01578499)

Last Updated: 2021-01-05

Results Overview

ORR4 was determined by an Independent Review Facility (IRF) based on Global Response Score (GRS) which consisted of a skin assessment by the investigator using the modified severity-weighted assessment tool (mSWAT), nodal and visceral radiographic assessment by an IRF and for the participants with mycosis fungoides (MF) only, detection of circulation Sezary cells. Participants whose first response occurred after the start of subsequent anticancer therapy were excluded. Response Criteria was based on International Society for Cutaneous Lymphomas (ISCL), United States Cutaneous Lymphoma Consortium (USCLC) and Cutaneous Lymphoma Task Force (CLTF) of the European Organisation for Research and Treatment of Cancer (EORTC) Consensus guidelines (Olsen, 2011).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

131 participants

Primary outcome timeframe

Each Cycle until disease progression, death End of treatment (Median overall follow-up 38.8 months)

Results posted on

2021-01-05

Participant Flow

Participants took part in the study at 34 investigative sites in Australia, Belgium, Brazil, France, Germany, Italy, Poland, Spain, Switzerland, United Kingdom, United States from 11 June 2012 to the Primary Completion data of 06 July 2018.

Participants with a diagnosis of cluster of differentiation antigen 30 (CD30)-Positive Cutaneous T-Cell Lymphoma were enrolled equally in 1 of 2 arms: brentuximab vedotin 1.8 mg/kg or physician's choice (Methotrexate or Bexarotene).

Participant milestones

Participant milestones
Measure	Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Overall Study STARTED	66	65
Overall Study Safety Population: Treated	66	62
Overall Study Intent to Treat Population: CD30+	64	64
Overall Study COMPLETED	32	22
Overall Study NOT COMPLETED	34	43

Reasons for withdrawal

Reasons for withdrawal
Measure	Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Overall Study Reason not Specified	0	1
Overall Study Lost to Follow-up	2	1
Overall Study Withdrawal by Subject	10	16
Overall Study Death	20	25
Overall Study Died and End of Study Page not Completed	2	0

Baseline Characteristics

Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Each Cycle until disease progression, death End of treatment (Median overall follow-up 38.8 months)

Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=64 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=64 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Percentage of Participants Achieving an Objective Response That Lasts at Least 4 Months (ORR4)	54.7 percentage of participants Interval 42.5 to 66.9	12.5 percentage of participants Interval 4.4 to 20.6

SECONDARY outcome

Timeframe: Each Cycle until disease progression, death or data cutoff (Median overall follow-up 38.8 months)

Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.

Complete Response (CR) was determined by the IRF based on Global Response Score (GRS) which consisted of a skin assessment by the investigator using the modified severity-weighted assessment tool (mSWAT), nodal and visceral radiographic and for the participants with mycosis fungoides (MF) only, detection of circulation Sezary cells. Response Criteria was based on ISCL, USCLC and CLTF of the EORTC Consensus guidelines (Olsen, 2011).

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=64 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=64 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Percentage of Participants Achieving a CR	17.2 percentage of participants Interval 7.9 to 26.4	1.6 percentage of participants Interval 0.0 to 8.4

SECONDARY outcome

Timeframe: Until disease progression, death or data cutoff (Median PFS follow-up of 38.8 months)

Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.

PFS was assessed by the IRF and is defined as the time from randomization until disease progression or death due to any cause, whichever occurs first. Disease progression was based on ISCL, USCLC and CLTF of the EORTC Consensus guidelines (Olsen, 2011).

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=64 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=64 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Progression-Free Survival (PFS)	16.7 months Interval 15.4 to 21.6	3.5 months Interval 2.4 to 4.6

SECONDARY outcome

Timeframe: Baseline up to End of Treatment (Week 52)

Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment. Here number of participants analyzed are participants evaluable for this outcome measure.

Skindex-29 is a 29-item dermatology-specific health-related quality of life (HRQoL). The Skindex-29 incorporates a 28-day recall period and consists of 3 domains: symptoms, emotions, and functioning. The domain scores and an overall score are expressed on a 100-point scale, from 0 to 100 with higher scores indicating lower levels of health- HRQoL. A negative change (reduction) from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=58 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=54 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Maximum Change From Baseline in Symptom Domain Score of the Skindex-29 Questionnaire	-28.08 score on a scale Standard Deviation 26.863	-8.62 score on a scale Standard Deviation 17.013

SECONDARY outcome

Timeframe: Until disease progression, death or data cutoff (Median follow-up 38.8 months)

Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment. Responders in ITT population were analyzed in this outcome measure.

Duration of response was assessed by the IRF in participants with confirmed response \[CR or Partial Response (PR)\] and is defined as the time between first documentation of response and disease progression. Response Criteria was based on ISCL, USCLC and CLTF of the EORTC Consensus guidelines (Olsen, 2011).

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=42 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=13 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Duration of Response (DOR)	15.1 months Interval 9.8 to 25.5	18.4 months Interval 3.5 to Upper limit of Confidence Interval (CI) was not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: Until disease progression, death or data cutoff (Median follow-up 38.8 months)

Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment. Skin responders in ITT population were analyzed in this outcome measure.

Duration of skin response (CR and PR) was assessed by the investigator and is defined as the time between the first skin response to progressive disease in skin. Per mSWAT, CR is defined as 100% clearance of skin lesions. PR is defined as 50%-99% clearance of skin disease from Baseline; No new tumors in participants without tumors at Baseline -MF; No new tumors-primary cutaneous anaplastic large cell lymphoma (pcALCL).Progressive disease is defined as ≥ 25% increase in skin disease from baseline, or loss of response: in those with CR or PR, increase of skin score of greater than the sum of nadir plus 50% baseline score, or new tumors in participants without tumors at baseline (MF).

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=47 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=19 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
DOR of Skin Response	18.9 months Interval 15.0 to 25.7	18.3 months Interval 3.5 to Upper limit of Confidence Interval (CI) was not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: From randomization until disease progression, death or data cutoff (Median follow-up 36.8 months)

Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.

EFS was assessed by the IRF and is defined as the time from randomization until any cause of treatment failure: disease progression, discontinuation of treatment for any reason, or death due to any cause, whichever occurs first. Disease progression was based on ISCL, USCLC and CLTF of the EORTC Consensus guidelines (Olsen, 2011).

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=64 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=64 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Event-Free Survival (EFS)	9.4 months Interval 5.9 to 11.7	2.3 months Interval 1.7 to 3.5

SECONDARY outcome

Timeframe: Day 1 pre-dose and 30 minutes after infusion in Cycles 1 and 3

Population: The pharmacokinetic (PK) population included participants with sufficient dose and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=16 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=50 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Cmax: Maximum Observed Concentration for Brentuximab Vedotin Cycle 1 Day 1	38.36 ug/mL Standard Deviation 9.427	38.40 ug/mL Standard Deviation 8.912
Cmax: Maximum Observed Concentration for Brentuximab Vedotin Cycle 3 Day 1	40.14 ug/mL Standard Deviation 12.697	36.69 ug/mL Standard Deviation 14.249

SECONDARY outcome

Timeframe: Day 1 pre-dose of Cycles 2 and 4

Population: The PK population included participants with sufficient dose and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=16 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=50 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin Cycle 2 Day 1	3.57 ug/mL Standard Deviation 10.101	0.58 ug/mL Standard Deviation 0.517
Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin Cycle 4 Day 1	0.99 ug/mL Standard Deviation 0.528	0.78 ug/mL Standard Deviation 0.446

SECONDARY outcome

Timeframe: Day 1 pre-dose and 30 minutes after infusion ended in Cycles 1 and 3

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=16 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=50 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Cmax: Maximum Observed Concentration for Monomethyl Auristatin (MMAE) for Brentuximab Vedotin Cycle 1 Day 1	2.53 ng/mL Standard Deviation 1.382	3.34 ng/mL Standard Deviation 1.901
Cmax: Maximum Observed Concentration for Monomethyl Auristatin (MMAE) for Brentuximab Vedotin Cycle 3 Day 1	2.96 ng/mL Standard Deviation 1.176	3.08 ng/mL Standard Deviation 1.276

SECONDARY outcome

Timeframe: Day 1 pre-dose of Cycles 2 and 4

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=16 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=50 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Ctrough: Observed Concentration at the End of a Dosing Interval for MMAE for Brentuximab Vedotin Cycle 4 Day 1	0.14 ng/mL Standard Deviation 0.113	0.11 ng/mL Standard Deviation 0.091
Ctrough: Observed Concentration at the End of a Dosing Interval for MMAE for Brentuximab Vedotin Cycle 2 Day 1	0.11 ng/mL Standard Deviation 0.095	0.09 ng/mL Standard Deviation 0.060

SECONDARY outcome

Timeframe: Baseline up to End of Treatment (Week 52)

Population: The Safety population included participants who received at least one dose of study drug.

Blood was collected and evaluated for ATA and neutralizing ATA in all participants who received brentuximab vedotin to assess immunogenicity.

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=16 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=50 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin Immunogenicity-evaluable participants	14 participants	46 participants
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin Baseline Positive: Transiently Positive	0 participants	3 participants
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin Baseline Positive: Persistently Positive	0 participants	0 participants
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin Baseline Negative: ATA negative	8 participants	23 participants
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin Baseline Negative: ATA positive	6 participants	19 participants
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin Baseline Negative: Transiently Positive	4 participants	9 participants
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin Baseline Negative: Persistently Positive	2 participants	10 participants
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin Baseline Negative: Neutralizing ATA Positive	4 participants	14 participants
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin Baseline Positive: ATA Negative	0 participants	1 participants
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin Baseline Positive: ATA Positive	0 participants	3 participants
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin Baseline Positive: Neutralizing ATA Positive	0 participants	2 participants

SECONDARY outcome

Timeframe: Day 1 of Cycles 1, 2, 4, 6, 8, 10, 12, 14, 16, at End of Treatment (EOT) and during posttreatment long treatment follow-up (LTFU) - (Median follow-up 38.8 months)

Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.

Skindex-29 is a 29-item dermatology-specific health-related quality of life (HRQoL). The Skindex-29 incorporates a 28-day recall period and consists of 3 domains: symptoms, emotions, and functioning. The domain scores and an overall score are expressed on a 100-point scale, 0 to 100 with higher scores indicating lower levels of health- HRQoL. A negative change (reduction) from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=64 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=64 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at 24-27 months LTFU	-17.04 score on a scale Standard Deviation 15.982	-9.05 score on a scale Standard Deviation 23.990
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at >30 months LTFU	-11.49 score on a scale Standard Deviation 22.470	-1.07 score on a scale Standard Deviation 18.886
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at Cycle 2	-5.44 score on a scale Standard Deviation 11.055	-2.49 score on a scale Standard Deviation 11.959
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at Cycle 4	-14.60 score on a scale Standard Deviation 17.488	-6.71 score on a scale Standard Deviation 9.755
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at Cycle 6	-17.59 score on a scale Standard Deviation 17.770	-5.40 score on a scale Standard Deviation 9.758
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at Cycle 8	-21.73 score on a scale Standard Deviation 18.882	-7.28 score on a scale Standard Deviation 16.769
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at Cycle 16	-19.35 score on a scale Standard Deviation 18.911	0.75 score on a scale Standard Deviation 10.308
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at End of Treatment	-16.26 score on a scale Standard Deviation 23.281	-0.96 score on a scale Standard Deviation 18.973
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at 3-6 months LTFU	-1.07 score on a scale Standard Deviation 3.704	-9.48 score on a scale Standard Deviation 21.629
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at 6-9 months LTFU	-8.04 score on a scale Standard Deviation 8.800	-9.68 score on a scale Standard Deviation 17.789
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at 18-21 months LTFU	-19.27 score on a scale Standard Deviation 20.962	-5.46 score on a scale Standard Deviation 16.679
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at 21-24 months LTFU	-16.60 score on a scale Standard Deviation 19.875	-6.86 score on a scale Standard Deviation 14.991
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at 27-30 months LTFU	-12.45 score on a scale Standard Deviation 19.639	-7.97 score on a scale Standard Deviation 16.401
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at Cycle 10	-22.47 score on a scale Standard Deviation 21.722	-3.71 score on a scale Standard Deviation 21.752
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at Cycle 12	-23.37 score on a scale Standard Deviation 21.555	-5.22 score on a scale Standard Deviation 17.704
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at Cycle 14	-19.72 score on a scale Standard Deviation 20.980	-7.49 score on a scale Standard Deviation 22.463
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at 9-12 months LTFU	-7.94 score on a scale Standard Deviation 15.582	-4.93 score on a scale Standard Deviation 14.516
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at 12-15 months LTFU	-16.21 score on a scale Standard Deviation 18.438	-11.16 score on a scale Standard Deviation 18.183
Change From Baseline in the Skindex-29 Questionnaire Total Score Change at 15-18 months LTFU	-19.18 score on a scale Standard Deviation 19.475	-8.53 score on a scale Standard Deviation 12.768

SECONDARY outcome

Timeframe: Day 1 of Cycles 1, 2, 4, 6, 8, 10, 12, 14, 16, at EOT and during posttreatment (LTFU) - (Median follow-up 38.8 months)

FACT-G is a 27-item general cancer QOL instrument completed by participants receiving cancer treatment. FACT-G incorporates a 7-day recall period and contains 4 primary subscales: Physical Well-Being (PWB; sum of 7 items, point range 0-28); Social/Family Well-Being (SWB, sum of 7-items, point range 0-28); Emotional Well-Being (EWB; sum of 6-items, point range 0-24); Functional Well-Being (FWB; sum of 7-items, point range 0-28); Fact-G total score=sum of PWB, SWB, EWB, FWB, point range 0-108. Higher scores for the total scales and subscales indicate better quality of life. A negative change (reduction) from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=64 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=64 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at Cycle 2	1.43 score on a scale Standard Deviation 10.168	-0.37 score on a scale Standard Deviation 11.723
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at Cycle 4	1.75 score on a scale Standard Deviation 12.014	1.78 score on a scale Standard Deviation 10.740
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at Cycle 6	4.23 score on a scale Standard Deviation 14.257	2.24 score on a scale Standard Deviation 13.108
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at Cycle 8	5.96 score on a scale Standard Deviation 16.030	2.54 score on a scale Standard Deviation 10.809
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at Cycle 10	6.61 score on a scale Standard Deviation 16.971	4.38 score on a scale Standard Deviation 15.040
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at Cycle 12	7.94 score on a scale Standard Deviation 18.837	8.61 score on a scale Standard Deviation 21.024
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at Cycle 14	9.04 score on a scale Standard Deviation 14.104	10.75 score on a scale Standard Deviation 13.615
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at Cycle 16	5.08 score on a scale Standard Deviation 9.230	7.88 score on a scale Standard Deviation 23.432
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at End of Treatment	0.35 score on a scale Standard Deviation 16.067	-2.29 score on a scale Standard Deviation 17.171
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at 3-6 months LTFU	16.00 score on a scale Standard Deviation 18.385	-2.92 score on a scale Standard Deviation 8.367
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at 6-9 months LTFU	-0.19 score on a scale Standard Deviation 19.648	-2.59 score on a scale Standard Deviation 12.473
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at 9-12 months LTFU	3.62 score on a scale Standard Deviation 17.651	-5.32 score on a scale Standard Deviation 10.555
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at 27-30 months LTFU	-1.57 score on a scale Standard Deviation 17.488	1.93 score on a scale Standard Deviation 8.716
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at >30 months LTFU	-6.22 score on a scale Standard Deviation 15.222	-2.85 score on a scale Standard Deviation 5.518
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at 12-15 months LTFU	8.33 score on a scale Standard Deviation 14.918	-1.34 score on a scale Standard Deviation 11.905
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at 15-18 months LTFU	3.03 score on a scale Standard Deviation 12.618	2.94 score on a scale Standard Deviation 14.756
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at 18-21 months LTFU	3.35 score on a scale Standard Deviation 11.117	-0.19 score on a scale Standard Deviation 14.316
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at 21-24 months LTFU	1.51 score on a scale Standard Deviation 5.471	0.61 score on a scale Standard Deviation 14.505
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score Change at 24-27 months LTFU	4.20 score on a scale Standard Deviation 7.952	1.42 score on a scale Standard Deviation 17.870

SECONDARY outcome

Timeframe: First dose of study drug through 30 days after last dose of study drug (Up to 450 days)

Population: The Safety population included participants who received at least one dose of study drug.

AEs and SAEs were assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event.

Outcome measures

Outcome measures
Measure	Brentuximab Vedotin n=66 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=62 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	63 participants	56 participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	18 participants	18 participants

Adverse Events

Brentuximab Vedotin

Serious events: 18 serious events

Other events: 60 other events

Deaths: 22 deaths

Methotrexate or Bexarotene

Serious events: 18 serious events

Other events: 51 other events

Deaths: 25 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Publication restrictions are in place

Restriction type: OTHER

Measure	Brentuximab Vedotin n=66 Participants Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate or Bexarotene n=64 Participants Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m\^2, tablets, orally, once daily with meals for up to 48 weeks.	Total n=130 Participants Total of all reporting groups
Age, Continuous	59.4 years STANDARD_DEVIATION 13.80 • n=66 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	56.6 years STANDARD_DEVIATION 14.43 • n=62 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	58.0 years STANDARD_DEVIATION 14.12 • n=128 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.
Sex: Female, Male Female	33 Participants n=66 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	28 Participants n=62 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	61 Participants n=128 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.
Sex: Female, Male Male	33 Participants n=66 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	34 Participants n=62 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	67 Participants n=128 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.
Race/Ethnicity, Customized White	56 participants n=64 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.	53 participants n=64 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.	109 participants n=128 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.
Race/Ethnicity, Customized Black or African American	3 participants n=64 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.	3 participants n=64 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.	6 participants n=128 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.
Race/Ethnicity, Customized Asian	1 participants n=64 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.	5 participants n=64 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.	6 participants n=128 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.
Race/Ethnicity, Customized Not reported	2 participants n=64 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.	8 participants n=64 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.	10 participants n=128 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.
Race/Ethnicity, Customized Other	1 participants n=64 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.	2 participants n=64 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.	3 participants n=128 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.
Race/Ethnicity, Customized Hispanic or Latino	2 participants n=64 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.	6 participants n=64 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.	8 participants n=128 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.
Race/Ethnicity, Customized Not Hispanic or Latino	60 participants n=64 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.	50 participants n=64 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.	110 participants n=128 Participants • ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.
Region of Enrollment Australia	12 Participants n=66 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	8 Participants n=62 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	20 Participants n=128 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.
Region of Enrollment Belgium	4 Participants n=66 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	2 Participants n=62 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	6 Participants n=128 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.
Region of Enrollment France	4 Participants n=66 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	3 Participants n=62 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	7 Participants n=128 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.
Region of Enrollment Germany	3 Participants n=66 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	2 Participants n=62 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	5 Participants n=128 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.
Region of Enrollment Italy	12 Participants n=66 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	6 Participants n=62 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	18 Participants n=128 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.
Region of Enrollment Poland	2 Participants n=66 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	1 Participants n=62 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	3 Participants n=128 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.
Region of Enrollment Spain	2 Participants n=66 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	3 Participants n=62 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	5 Participants n=128 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.
Region of Enrollment Switzerland	3 Participants n=66 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	3 Participants n=62 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	6 Participants n=128 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.
Region of Enrollment United Kingdom	8 Participants n=66 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	15 Participants n=62 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	23 Participants n=128 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.
Region of Enrollment United States	14 Participants n=66 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	17 Participants n=62 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	31 Participants n=128 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.
Region of Enrollment Brazil	2 Participants n=66 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	2 Participants n=62 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.	4 Participants n=128 Participants • Safety population included participants who received at least 1 dose of study drug, analyzed according to the actual treatment received.