A Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Hodgkin Lymphoma

Objective response rate is defined as the percentage of participants with complete remission (CR) or partial remission (PR) as assessed by an independent review facility (IRF) using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.

Time frame: Baseline until disease progression, death or end of study (EOS) (Up to 24 months)

Population: Intent-to-Treat (ITT) Population included all participants who were enrolled in the study.

Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.

Time frame: Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months)

Population: Pharmacokinetic (PK)-evaluable Population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. Number analyzed is the number of participants with data available at the given time-point.

Complete remission rate is defined as percentage of participants with CR per IRF response assessment based on IWG criteria are reported. CR is defined as the disappearance of all evidence of disease.

Time frame: Baseline until disease progression, death or EOS (Up to approximately 6 years)

Population: ITT Population included all participants who were enrolled in the study. In the absence of confirmation of death, survival time is censored at the last date the participant is known to be alive, including study closure.

Duration of CR is defined as the time from the date of first documentation of a CR or to the date of first documentation of tumor progression or progressive disease (PD) per IRF assessment according to IWG criteria. CR is defined as the disappearance of all evidence of disease and PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir.

Time frame: From first documented complete remission until disease progression (up to approximately 6 years)

Population: ITT Population included all participants who were enrolled in the study. Duration of complete remission was censored on the date of last disease assessment documenting absence of PD for those that were lost to follow-up, withdrew consent, started a new anticancer therapy other than SCT, or discontinued treatment due to undocumented PD after last disease assessment. Only participants with CR were analyzed for this outcome measure.

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

Time frame: From first documented complete or partial remission until disease progression (Up to 24 months)

Population: ITT Population included all participants who were enrolled in the study. DOR was censored on the date of last disease assessment documenting absence of PD for those that were lost to follow-up, withdrew consent, started a new anticancer therapy other than stem cell transplantation (SCT), or discontinued treatment due to undocumented PD after last disease assessment. All responders were evaluated in this outcome measure.

Blood samples were collected and tested for MMAE serum concentrations.

Time frame: Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months)

Population: PK-evaluable Population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. Number analyzed is the number of participants with data available at the given time-point.

Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.

Time frame: From the first dose through 30 days after the last dose of study medication (Up to 24 months)

Population: Safety Population was defined as all enrolled participants who received at least one dose of brentuximab vedotin.

An 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 a serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. AEs Grade 3 and higher are severe.

Time frame: From first dose through 30 days after the last dose of study medication (Up to 24 months)

Population: Safety Population was defined as all enrolled participants who received at least one dose of brentuximab vedotin.

Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA development) using a laboratory test. Confirmed ATA-positive response was categorized as transient (defined as 1 or 2 post-Baseline confirmed ATA-positive responses) and persistent (defined as more than 2 post-Baseline confirmed ATA positive responses) and neutralizing ATA (nATA) status. The confirmed ATA-positive samples were assessed for ATA titer and delineated into having high or low titers.

Time frame: Day 1 of every 3-week cycle up to 16 cycles and EOT (Up to 24 months)

Population: Participants from the Safety Population, all enrolled participants who received at least one dose of brentuximab vedotin, with data available for analysis.

OS is the time in months from start of study treatment to date of death due to any cause.

Time frame: Every 3 months for 18 months after EOT, thereafter, every 6 months until the sooner of death, study closure, or 5 years after enrollment of the last participant (up to approximately 6 years)

Population: ITT Population included all participants who were enrolled in the study. In the absence of confirmation of death, survival time is censored at the last date the participant is known to be alive, including study closure.

Time frame: Baseline up to EOS (up to approximately 6 years)

Population: ITT Population included all participants who were enrolled in the study.

PFS is defined as time in months from start of study treatment to first documentation of objective tumor progression per IRF assessment or up to death due to any cause, whichever occurs first.

Time frame: Baseline until disease progression, death or end of treatment (EOT), and then every 3 months up to approximately 6 years

Population: ITT Population included all participants who were enrolled in the study. For a participant that has not progressed and has not died, PFS is censored at the last response assessment that is SD or better.

Blood samples were collected and tested for conjugated and unconjugated antibodies.

Time frame: Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months)

Population: PK-evaluable Population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. Number analyzed is the number of participants with data available at the given time-point.