Hodgkin Disease
Conditions
Keywords
Drug therapy, pediatric Hodgkin disease, frontline Hodgkin disease, advanced stage Hodgkin disease, pediatric lymphoma
Brief summary
The purpose of this study is to assess the safety, tolerability, and anti-tumor activity, as well as confirm the recommended dose of brentuximab vedotin (ADCETRIS) in combination with a multiagent chemotherapy regimen, doxorubicin (Adriamycin), vinblastine, and dacarbazine, in pediatric participants with advanced stage newly diagnosed classical CD30+ Hodgkin Lymphoma (HL).
Detailed description
The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat pediatric participants who have advanced stage, newly diagnosed, classical CD30+ HL. This study will assess the safety, tolerability, and anti-tumor activity, as well as recommended dose of brentuximab vedotin in combination with a multiagent chemotherapy regimen that is based on a current standard of care (SOC) first-line treatment regimen for newly diagnosed HL. The study will enroll approximately 55 evaluable participants. The study will be conducted in 2 phases, Phase 1 and Phase 2. Phase 1 study will enroll at least 6 participants to determine the recommended dose. Once the recommended dose is identified additional participants will be enrolled into phase 2 so that the total number of evaluable participants will be at least 55, including participants treated at recommended dose in Phase 1. Participants will be enrolled to the following initial dose cohort with an option to explore a reduced dose cohort at 36 mg/m\^2 if needed: • Brentuximab vedotin 48 mg/m\^2 in combination with doxorubicin, vinblastine, and dacarbazine. This multi-center trial will be conducted in the United States, Italy, Brazil and Japan. The overall time to participate in this study is approximately 55 months, including the follow-up period. Participants will be followed for a maximum of 30 days following the last dose of protocol therapy for a follow-up assessment and will be followed for survival and disease status every 12 weeks for 12 months, and then every 24 weeks until death or study closure or for up to 2 years from the date of the last participant enrolled.
Interventions
DRUGBrentuximab vedotin
Brentuximab vedotin infusion
DRUGDoxorubicin
Doxorubicin infusion
DRUGVinblastine
Vinblastine infusion
DRUGDacarbazine
Dacarbazine infusion
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Each participant must meet all the following inclusion criteria to be enrolled in the study: 1. Histologically confirmed CD30+ classical HL. 2. Advanced stage, newly diagnosed HL (Stage III and Stage IV disease). 3. Treatment-naive HL. 4. Have performance scores of greater than or equal to (\>=) 50 for Lansky Play-performance or Karnofsky Performance Status. 5. Have bidimensional measurable disease as documented by radiographic technique per International Working Group (IWG) criteria. 6. Have adequate blood counts, renal and liver function as defined in the protocol.
Exclusion criteria
1. Nodular lymphocyte predominant HL. 2. Known active cerebral/meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML. 3. Any sensory or motor peripheral neuropathy. 4. Symptomatic neurologic disease compromising normal activities of daily living or requiring medications. 5. Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks before the first study protocol therapy. 6. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or any component of AVD. 7. Known human immunodeficiency virus positive. 8. Known hepatitis B surface antigen positive or known or suspected active hepatitis C infection, as determined by hepatitis B DNA or hepatitis C RNA, respectively, in blood. 9. Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. 10. Use of any strong or listed moderate cytochrome P450 (CYP) 3A4 inhibitors less than (\<) 2 weeks before the first dose of protocol therapy (please refer to the Study Manual for an example list of prohibited CYP3A4 inhibitors). 11. Any of the following cardiovascular conditions or values within 6 months before the first dose of protocol therapy: * Shortening fraction of \<27 percent (%) by echocardiogram or, if echocardiogram not feasible, ejection fraction of \<50% by radionuclide angiogram (RNA or MUGA \[multiple-gated acquisition scan\]). * New York Heart Association Class III or IV heart failure. * Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Recommended Dose of Brentuximab Vedotin in Combination With Doxorubicin, Vinblastine, and Dacarbazine in a Pediatric Population | From the first dose (Cycle 1) up to Day 56 (Cycle length=28 days) | The recommended dose was determined after considering all safety data in phase 1 and assessing for dose limiting toxicities (DLTs) which are defined as the dose range at which less than or equal to (\<=) 1 of 6 evaluable participants experience DLT within the defined observation period (Cycle 1 + 28 days). This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 1: Percentage of Participants Who Experienced Adverse Events (AEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy | From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days) | AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 1: Percentage of Participants Who Experienced Serious Adverse Events (SAEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy | From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days) | AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in death, Is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, Is a congenital anomaly/birth defect, Is a medically important event. |
| Phase 2: Percentage of Participants Who Achieved a Complete Remission (CR) Per Independent Review Facility (IRF) Assessment Per International Working Group (IWG) Criteria at End of Treatment (EOT) Visit | At end of treatment (EOT) visit 30 days after the last dose of study drug (at Month 7) | CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in the statistical analysis plan (SAP) , data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Percentage of Participants Whose Disease Was Positron Emission Tomography (PET) Negative After 2 Cycles of Protocol Therapy Per IRF Assessment | From first dose of study drug up to Cycle 2 Day 25 (Each Cycle length=28 days) | The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET negative after Cycle 2 was defined as an IRF Deauville score of (1 or 2 or 3). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Percentage of Participants Who Achieved a Partial Remission (PR) Per IRF Assessment Per IWG Criteria at EOT Visit | At EOT visit 30 days after the last dose of study drug (at Month 7) | PR was defined as regression of measurable disease and no new sites as assessed by IRF as per IWG criteria. Percentage of participants in the response-evaluable population who achieved a partial response based on the IRF assessment at the EOT visit based on the IWG criteria are reported. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Percentage of Participants Who Achieved an Overall Response Rate (ORR) Per IRF Assessment Per IWG Criteria at EOT Visit | At EOT visit 30 days after the last dose of study drug (at Month 7) | Overall response rate was defined as the percentage of participants with CR or PR as assessed by IRF using IWG criteria. CR was defined as the disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new diseases. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Percentage of Participants Who Were Able to Complete 6 Cycles of Protocol Therapy at the Recommended Dose | From first dose of study drug up to Cycle 6 (Each Cycle length=28 days) | This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Percentage of Participants Who Achieved an ORR Per IRF Assessment Per IWG Criteria at EOT Visit | At EOT visit 30 days after the last dose of study drug (at Month 7) | Overall response rate was defined as the percentage of participants with CR or PR as assessed by an IRF using IWG Revised Response Criteria. CR was defined as the disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 1: Percentage of Participants Whose Disease Was PET Negative After 2 Cycles of Protocol Therapy Per IRF Assessment | From first dose of study drug up to Cycle 2 (Each Cycle length=28 days) | The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET negative after Cycle 2 was defined as an IRF Deauville score of (1 or 2 or 3). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 1: Percentage of Participants Whose Disease Was PET Positive After 6 Cycles of Protocol Therapy Per IRF Assessment | From first dose of study drug up to Cycle 6 (Each Cycle length=28 days) | The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET positive after Cycle 6 defined as an IRF Deauville score of (4 or 5). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 1: Percentage of Participants Who Were Antitherapeutic Antibody (ATA) Positive, Persistently Positive or Transiently Positive, and Neutralizing Antitherapeutic Antibody (nATA) Positive | Up to 7 months | ATA positive was defined as participants who have a positive ATA in any postbaseline sample. Transiently ATA positive was defined as participants who have positive ATA in 1 or 2 postbaseline samples. Persistently ATA positive was defined as participants who have positive ATA in more than 2 postbaseline timepoints. Transiently ATA positive was defined as participants who have positive ATA in 1 or 2 postbaseline samples. nATA positive was defined as participants who have at least one positive nATA in any postbaseline ATA positive sample. Here, percentage of participants who were transiently or persistently ATA positive are considered as ATA positive. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 2: Progression-free Survival (PFS) | Up to 24 months | PFS per IRF:time from first dose until disease progression per IRF/death due to any cause,whichever occurred first.Participants with no objective progressive disease (PD),did not die,were still on study follow-up at time of analysis were removed from study prior to documentation of PD,PFS was censored on date of last adequate disease assessment before initiation of any non-protocol,alternative therapy.Participants who were on antitumor treatment,other than SCT/radiotherapy,censoring was at last adequate disease assessment before initiation of such alternative treatment.If participant experienced disease progression per IRF/died after initiation of antitumor treatment,other than SCT/radiotherapy,such participant was censored and not considered having PFS.Outcome measure was planned to be assessed for all participant treated at recommended dose in Phase 2.As per SAP,Phase 2 data was summarized and reported in two arms:Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Event-free Survival (EFS) | Up to 24 months | EFS:Time from first dose until any treatment failure:PD per IRF including progression events during follow-up period,failing to complete 6 cycles of treatment due to any reason or death due to any cause,whichever occurred first.EFS per IRF were censored on last adequate disease assessment date per IRF if none of above events occur during study.Participants with antitumor treatment,other than SCT/radiotherapy as part of frontline treatment were censored at last adequate disease assessment before initiation of such alternative treatment.If a participant experienced disease progression per IRF/died after initiation of antitumor treatment,other than SCT/radiotherapy,such participant was censored,and not be considered having EFS.This outcome measure was planned to be assessed for all patients treated at recommended dose in Phase 2.As prespecified in SAP,data for Phase 2 was summarized and reported in two arms:Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Overall Survival (OS) | Up to 24 months | Overall survival was defined as time from first dose until death. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive, including study closure. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Duration of Response (DOR) | Up to 24 months | DOR per IRF in participants with a response (CR or PR per IRF) was defined as the time from start of the first objective tumor response (CR or PR per IRF) to the first subsequent PD or death due to any cause, whichever occurred first. For patients who did not have an objective PD, did not die and are either still on a study follow-up at the time of the analysis, or were removed from the study prior to documentation of PD, DOR has been censored on the date of last adequate disease assessment. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 1: Number of ATA Positive and ATA Negative Participants With AEs and SAEs | Up to 24 months | This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 2: Percentage of Participants Receiving Irradiation for HL Following Study Treatment | Up to 24 months | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Percentage of Participants Who Experienced AEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy | From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days) | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Percentage of Participants Who Experienced SAEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy | From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days) | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Percentage of Participants Who Were ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive | From first dose until 30 days after the last dose of study drug (up to 7 months) | ATA positive was defined as participants who have a positive ATA in any postbaseline sample. Transiently ATA positive was defined as participants who have positive ATA in 1 or 2 postbaseline samples. Persistently ATA positive was defined as participants who have positive ATA in more than 2 postbaseline timepoints. Transiently ATA positive was defined as participants who have positive ATA in 1 or 2 postbaseline samples. nATA positive was defined as participants who have at least one positive nATA in any postbaseline ATA positive sample. Here, percentage of participants who were transiently or persistently ATA positive are considered as ATA positive. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Mean Plasma Cmax of MMAE | Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Mean Plasma AUC0-15 of MMAE | Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Median Tmax of MMAE in Plasma | Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Percentage of Participants Who Experienced Peripheral Neuropathy, Regardless of Seriousness, From the First Dose of Protocol Therapy | Up to 24 months | Peripheral Neuropathy (PN) was defined by the peripheral neuropathy standardized MedDRA query (SMQ) broad search. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Time to Onset and Resolution for All Peripheral Neuropathy Events | Up to 24 months | Time to onset of first event was defined as time from first dose of study drug to onset of first treatment-emergent PN event. Time to resolution was calculated as the time from onset date to the date of resolution PN (SMQ) event. Participants with multiple resolved events were counted once at the longest time to resolution. Resolution was defined as an event outcome of resolved or resolved with sequelae. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Immune Reconstitution-Change From Baseline Immunoglobulin G Levels at End of Treatment (EOT) | Baseline and End of Treatment (Month 7) | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 1: Percentage of Participants With Low and High ATA Titer Values | Up to 6 months | High ATA titer was defined as participants who have at least one postbaseline ATA titer less than (\>) 25. Low ATA titer was defined as participants whose postbaseline ATA titer are all less than or equal to (\<=) 25. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 2: Percentage of Participants With Low and High ATA Titer Values | Up to 6 months | High ATA titer was defined as participants who have at least one postbaseline ATA titer \>25. Low ATA titer was defined as participants whose postbaseline ATA titer are all \<=25. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | Cycle 1 and 3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 1: Mean AUC 0-15d of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | Cycle 1 and 3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 1: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants | Up to 24 months | CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The data is reported per ATA status as categories. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin Total Conjugated and Therapeutic Antibody (TAb) | Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | Cycle 1-3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants | Up to 24 months | CR is defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs | Up to 24 months | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin M at the End of Treatment (EOT) | Baseline, EOT [Month 7] | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin A at EOT | Baseline, EOT [Month 7] | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Immune Reconstitution-Change From Baseline in Tetanus at EOT | Baseline, EOT [Month 7] | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Immune Reconstitution-Change From Baseline in Haemophilus Influenzae B Antibody, IgG at EOT | Baseline, EOT [Month 7] | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Immune Reconstitution-Change From Baseline Poliovirus Antibodies Ratio at EOT | Baseline, EOT [Month 7] | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Immune Reconstitution-Change From Baseline Total Immunoglobulin at EOT | Baseline, EOT [Month 7] | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Immune Reconstitution-Change From Baseline in Peripheral Blood CD34+A at EOT | Baseline, EOT [Month 7] | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Immune Reconstitution-Change From Baseline in Total Lymphocyte Count at EOT | Baseline, EOT [Month 7] | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Baseline, EOT [Month 7] | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Baseline, EOT [Month 7] | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | Cycle 1-3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. |
| Phase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Monomethyl Auristatin E (MMAE) | Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb | Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of MMAE | Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum | Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 1: Median Time to Reach Cmax (Tmax) of MMAE in Plasma | Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days) | This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 1: Percentage of Participants Who Achieved a CR Per IRF Assessment Per IWG Criteria at EOT Visit | At EOT visit 30 days after the last dose of study drug (at Month 7) | CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm. |
| Phase 1: Percentage of Participants Who Achieved a PR Per IRF Assessment Per IWG Criteria at EOT Visit | At EOT visit 30 days after the last dose of study drug (at Month 7) | PR was defined as regression of measurable disease and no new diseases as per IWG Criteria based on IRF. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm. |
Countries
Brazil, Italy, Japan, United States
Participant flow
Recruitment details
Participants with advanced stage newly diagnosed, classical CD30+ Hodgkin Lymphoma (HL) took part in the study at 14 investigative sites in the United States, Italy, Brazil and Japan from 06 September 2017 to data cut-off date: 24 September 2021. This study is ongoing for Post-Treatment Follow-Up (which includes Progression-Free Survival Follow-Up \[PFSFU\] and Overall Survival Follow-Up \[OSFU\]) and optional Long-Term Safety Follow-up.
Pre-assignment details
Participants with advanced stage newly diagnosed, classical CD30+ HL received brentuximab vedotin 48 mg/m\^2 in combination with doxorubicin, vinblastine, and dacarbazine(A+AVD). Data for Phase 2 endpoints is reported for participants enrolled in Phase 2 only and for all treated in Phase 2, including Phase 1 participants.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD Brentuximab vedotin 48 mg/m\^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m\^2, vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles. | 8 |
| Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD Brentuximab vedotin 48 mg/m\^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m\^2, vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles. | 51 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Particpants Ongoing in Long-Term Safety Follow-Up | 8 | 23 |
| Overall Study | Post-Treatment Follow-up (PFSFU and OSFU) | 0 | 28 |
Baseline characteristics
| Characteristic | Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Total | Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD |
|---|---|---|---|
| Age, Continuous | 13.9 years STANDARD_DEVIATION 2.88 | 13.7 years STANDARD_DEVIATION 3.03 | 12.4 years STANDARD_DEVIATION 3.81 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 23 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 32 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants | 12 Participants | 0 Participants |
| Race/Ethnicity, Customized Brown or Mulatto | 9 Participants | 9 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 26 Participants | 34 Participants | 8 Participants |
| Region of Enrollment Brazil | 29 Participants | 30 Participants | 1 Participants |
| Region of Enrollment Italy | 10 Participants | 15 Participants | 5 Participants |
| Region of Enrollment Japan | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment United States | 10 Participants | 12 Participants | 2 Participants |
| Sex: Female, Male Female | 24 Participants | 28 Participants | 4 Participants |
| Sex: Female, Male Male | 27 Participants | 31 Participants | 4 Participants |
| Weight | 49.91 kilograms (kg) STANDARD_DEVIATION 15.649 | 49.37 kilograms (kg) STANDARD_DEVIATION 16 | 45.91 kilograms (kg) STANDARD_DEVIATION 18.867 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 51 |
| other Total, other adverse events | 8 / 8 | 51 / 51 |
| serious Total, serious adverse events | 1 / 8 | 23 / 51 |
Outcome results
Primary
Phase 1: Percentage of Participants Who Experienced Adverse Events (AEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time frame: From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
Population: The safety population included participants who had received at least 1 dose of any study drug (A+AVD regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Percentage of Participants Who Experienced Adverse Events (AEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy | 100 percentage of participants |
Primary
Phase 1: Percentage of Participants Who Experienced Serious Adverse Events (SAEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in death, Is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, Is a congenital anomaly/birth defect, Is a medically important event.
Time frame: From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
Population: The safety population included participants who had received at least 1 dose of any study drug (A+AVD regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Percentage of Participants Who Experienced Serious Adverse Events (SAEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy | 13 percentage of participants |
Primary
Phase 1: Recommended Dose of Brentuximab Vedotin in Combination With Doxorubicin, Vinblastine, and Dacarbazine in a Pediatric Population
The recommended dose was determined after considering all safety data in phase 1 and assessing for dose limiting toxicities (DLTs) which are defined as the dose range at which less than or equal to (\<=) 1 of 6 evaluable participants experience DLT within the defined observation period (Cycle 1 + 28 days). This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time frame: From the first dose (Cycle 1) up to Day 56 (Cycle length=28 days)
Population: The DLT-evaluable population included participants who had received at least 1 dose of study drug therapy and experienced a DLT or no DLT during the DLT observation period. Participants who received granulocyte colony stimulating factor (G-CSF) during the DLT observation period were excluded from the DLT-Evaluable Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Recommended Dose of Brentuximab Vedotin in Combination With Doxorubicin, Vinblastine, and Dacarbazine in a Pediatric Population | 48 mg/m^2 |
Primary
Phase 2: Percentage of Participants Who Achieved a Complete Remission (CR) Per Independent Review Facility (IRF) Assessment Per International Working Group (IWG) Criteria at End of Treatment (EOT) Visit
CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in the statistical analysis plan (SAP) , data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: At end of treatment (EOT) visit 30 days after the last dose of study drug (at Month 7)
Population: Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants Who Achieved a Complete Remission (CR) Per Independent Review Facility (IRF) Assessment Per International Working Group (IWG) Criteria at End of Treatment (EOT) Visit | 75 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants Who Achieved a Complete Remission (CR) Per Independent Review Facility (IRF) Assessment Per International Working Group (IWG) Criteria at End of Treatment (EOT) Visit | 76 percentage of participants |
Primary
Phase 2: Percentage of Participants Who Achieved an Overall Response Rate (ORR) Per IRF Assessment Per IWG Criteria at EOT Visit
Overall response rate was defined as the percentage of participants with CR or PR as assessed by IRF using IWG criteria. CR was defined as the disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new diseases. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: At EOT visit 30 days after the last dose of study drug (at Month 7)
Population: Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants Who Achieved an Overall Response Rate (ORR) Per IRF Assessment Per IWG Criteria at EOT Visit | 86 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants Who Achieved an Overall Response Rate (ORR) Per IRF Assessment Per IWG Criteria at EOT Visit | 88 percentage of participants |
Primary
Phase 2: Percentage of Participants Who Achieved a Partial Remission (PR) Per IRF Assessment Per IWG Criteria at EOT Visit
PR was defined as regression of measurable disease and no new sites as assessed by IRF as per IWG criteria. Percentage of participants in the response-evaluable population who achieved a partial response based on the IRF assessment at the EOT visit based on the IWG criteria are reported. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: At EOT visit 30 days after the last dose of study drug (at Month 7)
Population: Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants Who Achieved a Partial Remission (PR) Per IRF Assessment Per IWG Criteria at EOT Visit | 12 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants Who Achieved a Partial Remission (PR) Per IRF Assessment Per IWG Criteria at EOT Visit | 12 percentage of participants |
Primary
Phase 2: Percentage of Participants Whose Disease Was Positron Emission Tomography (PET) Negative After 2 Cycles of Protocol Therapy Per IRF Assessment
The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET negative after Cycle 2 was defined as an IRF Deauville score of (1 or 2 or 3). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: From first dose of study drug up to Cycle 2 Day 25 (Each Cycle length=28 days)
Population: Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants Whose Disease Was Positron Emission Tomography (PET) Negative After 2 Cycles of Protocol Therapy Per IRF Assessment | 90 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants Whose Disease Was Positron Emission Tomography (PET) Negative After 2 Cycles of Protocol Therapy Per IRF Assessment | 90 percentage of participants |
Primary
Phase 2: Percentage of Participants Who Were Able to Complete 6 Cycles of Protocol Therapy at the Recommended Dose
This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: From first dose of study drug up to Cycle 6 (Each Cycle length=28 days)
Population: The safety population included participants who had received at least 1 dose of any study drug (A+AVD regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants Who Were Able to Complete 6 Cycles of Protocol Therapy at the Recommended Dose | 100 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants Who Were Able to Complete 6 Cycles of Protocol Therapy at the Recommended Dose | 100 percentage of participants |
Secondary
Phase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of MMAE
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of MMAE | Cycle 1 Day 1 | 29.8 day* nanogram per milliliter (day*ng/mL) | Standard Deviation 21.2 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of MMAE | Cycle 1 Day 15 | 13.1 day* nanogram per milliliter (day*ng/mL) | Standard Deviation 2.99 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of MMAE | Cycle 3 Day 1 | 8.88 day* nanogram per milliliter (day*ng/mL) | Standard Deviation 2.53 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of MMAE | Cycle 3 Day 15 | 7.17 day* nanogram per milliliter (day*ng/mL) | Standard Deviation 2.17 |
Secondary
Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb | AUC0-15d of Brentuximab Vedotin at Cycle 1 Day 1 | 42.3 day*microgram per milliliter(day*mcg/mL) | Standard Deviation 3.1 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb | AUC0-15d of Brentuximab Vedotin at Cycle 1 Day 15 | 48.8 day*microgram per milliliter(day*mcg/mL) | Standard Deviation 5.83 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb | AUC0-15d of Brentuximab Vedotin at Cycle 3 Day 1 | 72.7 day*microgram per milliliter(day*mcg/mL) | Standard Deviation 27.8 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb | AUC0-15d of Brentuximab Vedotin at Cycle 3 Day 15 | 64.8 day*microgram per milliliter(day*mcg/mL) | Standard Deviation 13.5 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb | AUC0-15d of TAb at Cycle 1 Day 1 | 80.6 day*microgram per milliliter(day*mcg/mL) | Standard Deviation 13 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb | AUC0-15d of TAb at Cycle 1 Day 15 | 103 day*microgram per milliliter(day*mcg/mL) | Standard Deviation 14.6 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb | AUC0-15d of TAb at Cycle 3 Day 1 | 127 day*microgram per milliliter(day*mcg/mL) | Standard Deviation 10.2 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb | AUC0-15d of TAb at Cycle 3 Day 15 | 128 day*microgram per milliliter(day*mcg/mL) | Standard Deviation 34.4 |
Secondary
Phase 1: Mean AUC 0-15d of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time frame: Cycle 1 and 3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean AUC 0-15d of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 1 Day 1 | 42.4 day*µg/mL | — |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean AUC 0-15d of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 1 Day 15 | 50.0 day*µg/mL | — |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean AUC 0-15d of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 3 Day 1 | 56.6 day*µg/mL | — |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean AUC 0-15d of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 3 Day 15 | 63.0 day*µg/mL | — |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean AUC 0-15d of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 1 Day 1 | 42.2 day*µg/mL | Standard Deviation 3.4 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean AUC 0-15d of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 1 Day 15 | 48.6 day*µg/mL | Standard Deviation 6.48 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean AUC 0-15d of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 3 Day 1 | 75.4 day*µg/mL | Standard Deviation 29.46 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean AUC 0-15d of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 3 Day 15 | 65.1 day*µg/mL | Standard Deviation 15.06 |
Secondary
Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time frame: Cycle 1 and 3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 1 Day 1 | 23.3 µg/mL | — |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 1 Day 15 | 21.1 µg/mL | — |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 3 Day 1 | 23.1 µg/mL | — |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 3 Day 15 | 21.6 µg/mL | — |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 1 Day 1 | 22.5 µg/mL | Standard Deviation 1.62 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 1 Day 15 | 23.5 µg/mL | Standard Deviation 4.17 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 3 Day 1 | 27.2 µg/mL | Standard Deviation 3.62 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 3 Day 15 | 28.3 µg/mL | Standard Deviation 7.32 |
Secondary
Phase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Monomethyl Auristatin E (MMAE)
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Monomethyl Auristatin E (MMAE) | Cycle 1 Day 1 | 5.51 nanogram per milliliter (ng/ml) | Standard Deviation 3.91 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Monomethyl Auristatin E (MMAE) | Cycle 1 Day 15 | 2.08 nanogram per milliliter (ng/ml) | Standard Deviation 0.677 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Monomethyl Auristatin E (MMAE) | Cycle 3 Day 1 | 1.38 nanogram per milliliter (ng/ml) | Standard Deviation 0.514 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Monomethyl Auristatin E (MMAE) | Cycle 3 Day 15 | 1.19 nanogram per milliliter (ng/ml) | Standard Deviation 0.366 |
Secondary
Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin Total Conjugated and Therapeutic Antibody (TAb)
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin Total Conjugated and Therapeutic Antibody (TAb) | Conjugate Brentuximab Vedotin at Cycle 1 Day 1 | 22.6 microgram per milliliter(mcg/mL) | Standard Deviation 1.51 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin Total Conjugated and Therapeutic Antibody (TAb) | Conjugate Brentuximab Vedotin at Cycle 1 Day 15 | 23.1 microgram per milliliter(mcg/mL) | Standard Deviation 3.85 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin Total Conjugated and Therapeutic Antibody (TAb) | Conjugate Brentuximab Vedotin at Cycle 3 Day 1 | 26.7 microgram per milliliter(mcg/mL) | Standard Deviation 3.65 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin Total Conjugated and Therapeutic Antibody (TAb) | Conjugate Brentuximab Vedotin at Cycle 3 Day 15 | 27.3 microgram per milliliter(mcg/mL) | Standard Deviation 7.14 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin Total Conjugated and Therapeutic Antibody (TAb) | TAb at Cycle 1 Day 1 | 24.9 microgram per milliliter(mcg/mL) | Standard Deviation 3.84 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin Total Conjugated and Therapeutic Antibody (TAb) | TAb at Cycle 1 Day 15 | 25.5 microgram per milliliter(mcg/mL) | Standard Deviation 5.28 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin Total Conjugated and Therapeutic Antibody (TAb) | TAb at Cycle 3 Day 1 | 29.6 microgram per milliliter(mcg/mL) | Standard Deviation 4.05 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin Total Conjugated and Therapeutic Antibody (TAb) | TAb at Cycle 3 Day 15 | 28.1 microgram per milliliter(mcg/mL) | Standard Deviation 7.45 |
Secondary
Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time frame: Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum | Tmax of TAb at Cycle 1 Day 1 | 1.00 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum | Tmax of Brentuximab Vedotin at Cycle 1 Day 1 | 1.00 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum | Tmax of Brentuximab Vedotin at Cycle 1 Day 15 | 0.915 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum | Tmax of Brentuximab Vedotin at Cycle 3 Day 1 | 1.00 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum | Tmax of Brentuximab Vedotin at Cycle 3 Day 15 | 0.830 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum | Tmax of TAb at Cycle 1 Day 15 | 0.915 hour |
Secondary
Phase 1: Median Time to Reach Cmax (Tmax) of MMAE in Plasma
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Median Time to Reach Cmax (Tmax) of MMAE in Plasma | Cycle 1 Day 1 | 44.9 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Median Time to Reach Cmax (Tmax) of MMAE in Plasma | Cycle 1 Day 15 | 43.1 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Median Time to Reach Cmax (Tmax) of MMAE in Plasma | Cycle 3 Day 1 | 48.0 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Median Time to Reach Cmax (Tmax) of MMAE in Plasma | Cycle 3 Day 15 | 48.2 hour |
Secondary
Phase 1: Number of ATA Positive and ATA Negative Participants With AEs and SAEs
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time frame: Up to 24 months
Population: The Safety Population included participants who received at least 1 dose of any drug in the A+AVD regimen, with data available for analyses. Data is reported as per ATA positive and negative status.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Number of ATA Positive and ATA Negative Participants With AEs and SAEs | ATA Negative: AEs | 7 Participants |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Number of ATA Positive and ATA Negative Participants With AEs and SAEs | ATA Positive: AEs | 1 Participants |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Number of ATA Positive and ATA Negative Participants With AEs and SAEs | ATA Negative: SAEs | 0 Participants |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Number of ATA Positive and ATA Negative Participants With AEs and SAEs | ATA Positive: SAEs | 1 Participants |
Secondary
Phase 1: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants
CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The data is reported per ATA status as categories. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time frame: Up to 24 months
Population: Immunogenicity population included participants who received at least 1 dose of study drug and had the baseline immunogenicity sample and at least 1 postbaseline immunogenicity sample assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants | ATA Negative who Achieved CR | 86 percentage of participants |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants | Transiently ATA Positive who Achieved CR | 100 percentage of participants |
Secondary
Phase 1: Percentage of Participants Who Achieved a CR Per IRF Assessment Per IWG Criteria at EOT Visit
CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm.
Time frame: At EOT visit 30 days after the last dose of study drug (at Month 7)
Population: Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Percentage of Participants Who Achieved a CR Per IRF Assessment Per IWG Criteria at EOT Visit | 88 percentage of participants |
Secondary
Phase 1: Percentage of Participants Who Achieved an ORR Per IRF Assessment Per IWG Criteria at EOT Visit
Overall response rate was defined as the percentage of participants with CR or PR as assessed by an IRF using IWG Revised Response Criteria. CR was defined as the disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm.
Time frame: At EOT visit 30 days after the last dose of study drug (at Month 7)
Population: Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Percentage of Participants Who Achieved an ORR Per IRF Assessment Per IWG Criteria at EOT Visit | 100 percentage of participants |
Secondary
Phase 1: Percentage of Participants Who Achieved a PR Per IRF Assessment Per IWG Criteria at EOT Visit
PR was defined as regression of measurable disease and no new diseases as per IWG Criteria based on IRF. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm.
Time frame: At EOT visit 30 days after the last dose of study drug (at Month 7)
Population: Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Percentage of Participants Who Achieved a PR Per IRF Assessment Per IWG Criteria at EOT Visit | 13 percentage of participants |
Secondary
Phase 1: Percentage of Participants Whose Disease Was PET Negative After 2 Cycles of Protocol Therapy Per IRF Assessment
The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET negative after Cycle 2 was defined as an IRF Deauville score of (1 or 2 or 3). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm.
Time frame: From first dose of study drug up to Cycle 2 (Each Cycle length=28 days)
Population: Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Percentage of Participants Whose Disease Was PET Negative After 2 Cycles of Protocol Therapy Per IRF Assessment | 88 percentage of participants |
Secondary
Phase 1: Percentage of Participants Whose Disease Was PET Positive After 6 Cycles of Protocol Therapy Per IRF Assessment
The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET positive after Cycle 6 defined as an IRF Deauville score of (4 or 5). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm.
Time frame: From first dose of study drug up to Cycle 6 (Each Cycle length=28 days)
Population: This outcome measure was planned to be assessed only for participants treated in Phase 1 arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Percentage of Participants Whose Disease Was PET Positive After 6 Cycles of Protocol Therapy Per IRF Assessment | 13 percentage of participants |
Secondary
Phase 1: Percentage of Participants Who Were Antitherapeutic Antibody (ATA) Positive, Persistently Positive or Transiently Positive, and Neutralizing Antitherapeutic Antibody (nATA) Positive
ATA positive was defined as participants who have a positive ATA in any postbaseline sample. Transiently ATA positive was defined as participants who have positive ATA in 1 or 2 postbaseline samples. Persistently ATA positive was defined as participants who have positive ATA in more than 2 postbaseline timepoints. Transiently ATA positive was defined as participants who have positive ATA in 1 or 2 postbaseline samples. nATA positive was defined as participants who have at least one positive nATA in any postbaseline ATA positive sample. Here, percentage of participants who were transiently or persistently ATA positive are considered as ATA positive. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time frame: Up to 7 months
Population: Immunogenicity population included participants who received at least 1 dose of study drug and had the baseline immunogenicity sample and at least 1 postbaseline immunogenicity sample assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Percentage of Participants Who Were Antitherapeutic Antibody (ATA) Positive, Persistently Positive or Transiently Positive, and Neutralizing Antitherapeutic Antibody (nATA) Positive | Transiently ATA Positive | 13 percentage of participants |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Percentage of Participants Who Were Antitherapeutic Antibody (ATA) Positive, Persistently Positive or Transiently Positive, and Neutralizing Antitherapeutic Antibody (nATA) Positive | Persistently ATA Positive | 0 percentage of participants |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Percentage of Participants Who Were Antitherapeutic Antibody (ATA) Positive, Persistently Positive or Transiently Positive, and Neutralizing Antitherapeutic Antibody (nATA) Positive | nATA Positive | 0 percentage of participants |
Secondary
Phase 1: Percentage of Participants With Low and High ATA Titer Values
High ATA titer was defined as participants who have at least one postbaseline ATA titer less than (\>) 25. Low ATA titer was defined as participants whose postbaseline ATA titer are all less than or equal to (\<=) 25. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time frame: Up to 6 months
Population: Immunogenicity population included participants who received at least 1 dose of study drug and had the baseline immunogenicity sample and at least 1 postbaseline immunogenicity sample assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Percentage of Participants With Low and High ATA Titer Values | ATA Titer low | 13 percentage of participants |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 1: Percentage of Participants With Low and High ATA Titer Values | ATA Titer High | 0 percentage of participants |
Secondary
Phase 2: Duration of Response (DOR)
DOR per IRF in participants with a response (CR or PR per IRF) was defined as the time from start of the first objective tumor response (CR or PR per IRF) to the first subsequent PD or death due to any cause, whichever occurred first. For patients who did not have an objective PD, did not die and are either still on a study follow-up at the time of the analysis, or were removed from the study prior to documentation of PD, DOR has been censored on the date of last adequate disease assessment. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Up to 24 months
Population: Response Evaluable Population=Participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment (assessments based on investigator assessments or assessments based on an independent review facility). For participants who do not have an objective PD and did not die at the last follow-up, DOR has been censored on the date of last adequate disease assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Duration of Response (DOR) | NA months |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Duration of Response (DOR) | NA months |
Secondary
Phase 2: Event-free Survival (EFS)
EFS:Time from first dose until any treatment failure:PD per IRF including progression events during follow-up period,failing to complete 6 cycles of treatment due to any reason or death due to any cause,whichever occurred first.EFS per IRF were censored on last adequate disease assessment date per IRF if none of above events occur during study.Participants with antitumor treatment,other than SCT/radiotherapy as part of frontline treatment were censored at last adequate disease assessment before initiation of such alternative treatment.If a participant experienced disease progression per IRF/died after initiation of antitumor treatment,other than SCT/radiotherapy,such participant was censored,and not be considered having EFS.This outcome measure was planned to be assessed for all patients treated at recommended dose in Phase 2.As prespecified in SAP,data for Phase 2 was summarized and reported in two arms:Phase 2 and Phase 1 + Phase 2.
Time frame: Up to 24 months
Population: The safety/efficacy population included participants who received at least 1 dose of any drug in the A+AVD regimen. For participants who do not have an objective PD and did not die at the last follow-up, EFS has been censored on the date of last adequate disease assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Event-free Survival (EFS) | NA months |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Event-free Survival (EFS) | NA months |
Secondary
Phase 2: Immune Reconstitution-Change From Baseline Immunoglobulin G Levels at End of Treatment (EOT)
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Baseline and End of Treatment (Month 7)
Population: Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Number analyzed= number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline Immunoglobulin G Levels at End of Treatment (EOT) | Baseline | 16.518 g/L | Standard Deviation 5.5306 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline Immunoglobulin G Levels at End of Treatment (EOT) | Change from Baseline at EOT | -4.822 g/L | Standard Deviation 4.8964 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline Immunoglobulin G Levels at End of Treatment (EOT) | Baseline | 16.217 g/L | Standard Deviation 5.2175 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline Immunoglobulin G Levels at End of Treatment (EOT) | Change from Baseline at EOT | -4.675 g/L | Standard Deviation 4.7204 |
Secondary
Phase 2: Immune Reconstitution-Change From Baseline in Haemophilus Influenzae B Antibody, IgG at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Baseline, EOT [Month 7]
Population: Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the number of participants with data available for analyses. Number analyzed= number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in Haemophilus Influenzae B Antibody, IgG at EOT | Baseline | 10.39 µg/mL | Standard Deviation 27.017 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in Haemophilus Influenzae B Antibody, IgG at EOT | Change from Baseline at EOT | -7.00 µg/mL | Standard Deviation 24.258 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in Haemophilus Influenzae B Antibody, IgG at EOT | Baseline | 9.50 µg/mL | Standard Deviation 25.167 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in Haemophilus Influenzae B Antibody, IgG at EOT | Change from Baseline at EOT | -6.03 µg/mL | Standard Deviation 23.16 |
Secondary
Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin A at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Baseline, EOT [Month 7]
Population: Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the participants with data available for analyses. Number analyzed= number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin A at EOT | Change from Baseline at EOT | -0.195 g/L | Standard Deviation 1.0479 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin A at EOT | Baseline | 2.708 g/L | Standard Deviation 1.2379 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin A at EOT | Change from Baseline at EOT | -0.125 g/L | Standard Deviation 1.0844 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin A at EOT | Baseline | 2.671 g/L | Standard Deviation 1.1879 |
Secondary
Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin M at the End of Treatment (EOT)
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Baseline, EOT [Month 7]
Population: Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation, with data available for analyses. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin M at the End of Treatment (EOT) | Baseline | 1.275 g/L | Standard Deviation 0.5065 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin M at the End of Treatment (EOT) | Change at EOT (Month 7) | -0.345 g/L | Standard Deviation 0.5942 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin M at the End of Treatment (EOT) | Baseline | 1.261 g/L | Standard Deviation 0.4824 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin M at the End of Treatment (EOT) | Change at EOT (Month 7) | -0.375 g/L | Standard Deviation 0.5766 |
Secondary
Phase 2: Immune Reconstitution-Change From Baseline in Peripheral Blood CD34+A at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Baseline, EOT [Month 7]
Population: Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the number of participants with data available for analyses. Number analyzed= number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in Peripheral Blood CD34+A at EOT | Baseline | 4.182 µL | Standard Deviation 4.1227 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in Peripheral Blood CD34+A at EOT | Change from Baseline at EOT | -1.512 µL | Standard Deviation 4.7075 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in Peripheral Blood CD34+A at EOT | Baseline | 3.917 µL | Standard Deviation 3.8917 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in Peripheral Blood CD34+A at EOT | Change from Baseline at EOT | -1.456 µL | Standard Deviation 4.3472 |
Secondary
Phase 2: Immune Reconstitution-Change From Baseline in Tetanus at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Baseline, EOT [Month 7]
Population: Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the number of participants with data available for analyses. Number analyzed =number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in Tetanus at EOT | Baseline | 1.636 (IU)/mL | Standard Deviation 2.56 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in Tetanus at EOT | Change from Baseline at EOT | -0.648 (IU)/mL | Standard Deviation 1.3412 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in Tetanus at EOT | Baseline | 1.935 (IU)/mL | Standard Deviation 3.0358 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in Tetanus at EOT | Change from Baseline at EOT | -0.914 (IU)/mL | Standard Deviation 2.2679 |
Secondary
Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Baseline, EOT [Month 7]
Population: Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the number of participants with data available for analyses. Number analyzed= number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Baseline: CD4+CD45RA-CD197- | 28.0 percentage of CD4+ subset cells | Standard Deviation 12.76 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD4+CD45RA-CD197- | -5.0 percentage of CD4+ subset cells | Standard Deviation 17.72 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Baseline: CD4+CD45RA-CD197+ | 23.7 percentage of CD4+ subset cells | Standard Deviation 14.33 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD4+CD45RA-CD197+ | 13.0 percentage of CD4+ subset cells | Standard Deviation 14.14 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Baseline: CD4+CD45RA+CD197- | 2.9 percentage of CD4+ subset cells | Standard Deviation 3.41 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD4+CD45RA+CD197- | -0.7 percentage of CD4+ subset cells | Standard Deviation 2.25 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Baseline: CD4+CD45RA+CD197+ | 46.2 percentage of CD4+ subset cells | Standard Deviation 14.44 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD4+CD45RA+CD197+ | -7.2 percentage of CD4+ subset cells | Standard Deviation 11.6 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD4+CD45RA+CD197+ | -6.8 percentage of CD4+ subset cells | Standard Deviation 11.04 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Baseline: CD4+CD45RA-CD197- | 29.0 percentage of CD4+ subset cells | Standard Deviation 13.42 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Baseline: CD4+CD45RA+CD197- | 3.1 percentage of CD4+ subset cells | Standard Deviation 3.22 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD4+CD45RA-CD197- | -5.1 percentage of CD4+ subset cells | Standard Deviation 16.44 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Baseline: CD4+CD45RA+CD197+ | 46.3 percentage of CD4+ subset cells | Standard Deviation 14.89 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Baseline: CD4+CD45RA-CD197+ | 22.3 percentage of CD4+ subset cells | Standard Deviation 13.86 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD4+CD45RA+CD197- | -0.7 percentage of CD4+ subset cells | Standard Deviation 2.41 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD4+CD45RA-CD197+ | 12.6 percentage of CD4+ subset cells | Standard Deviation 13.21 |
Secondary
Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Baseline, EOT [Month 7]
Population: Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the number of participants with data available for analyses. Number analyzed= number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Baseline: CD8+CD45RA+CD197- | 25.9 percentage of CD8+ subset cells | Standard Deviation 15.43 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Baseline: CD8+CD45RA-CD197+ | 2.4 percentage of CD8+ subset cells | Standard Deviation 1.81 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD8+CD45RA+CD197- | -6.0 percentage of CD8+ subset cells | Standard Deviation 11.27 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Baseline: CD8+CD45RA-CD197- | 39.9 percentage of CD8+ subset cells | Standard Deviation 19.32 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Baseline: CD8+CD45RA+CD197+ | 31.3 percentage of CD8+ subset cells | Standard Deviation 18 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD8+CD45RA-CD197+ | 1.6 percentage of CD8+ subset cells | Standard Deviation 2.52 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD8+CD45RA+CD197+ | 15.7 percentage of CD8+ subset cells | Standard Deviation 11.48 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD8+CD45RA-CD197- | -11.5 percentage of CD8+ subset cells | Standard Deviation 13.85 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD8+CD45RA+CD197+ | 15.4 percentage of CD8+ subset cells | Standard Deviation 12.15 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD8+CD45RA-CD197- | -11.0 percentage of CD8+ subset cells | Standard Deviation 14.33 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Baseline: CD8+CD45RA-CD197+ | 2.3 percentage of CD8+ subset cells | Standard Deviation 1.76 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD8+CD45RA-CD197+ | 2.1 percentage of CD8+ subset cells | Standard Deviation 3.08 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Baseline: CD8+CD45RA+CD197- | 25.8 percentage of CD8+ subset cells | Standard Deviation 14.6 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Change from Baseline at EOT: CD8+CD45RA+CD197- | -6.5 percentage of CD8+ subset cells | Standard Deviation 11.83 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Baseline: CD8+CD45RA+CD197+ | 30.8 percentage of CD8+ subset cells | Standard Deviation 18.53 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT | Baseline: CD8+CD45RA-CD197- | 40.6 percentage of CD8+ subset cells | Standard Deviation 20 |
Secondary
Phase 2: Immune Reconstitution-Change From Baseline in Total Lymphocyte Count at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Baseline, EOT [Month 7]
Population: Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in Total Lymphocyte Count at EOT | Baseline | 1.8022 10^9 lymphocytes/L | Standard Deviation 0.95206 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline in Total Lymphocyte Count at EOT | Change from Baseline at EOT | 0.6736 10^9 lymphocytes/L | Standard Deviation 3.77611 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in Total Lymphocyte Count at EOT | Baseline | 1.7408 10^9 lymphocytes/L | Standard Deviation 0.91394 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline in Total Lymphocyte Count at EOT | Change from Baseline at EOT | 0.5965 10^9 lymphocytes/L | Standard Deviation 3.50121 |
Secondary
Phase 2: Immune Reconstitution-Change From Baseline Poliovirus Antibodies Ratio at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Baseline, EOT [Month 7]
Population: Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the number of participants with data available for analyses. Number analyzed= number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline Poliovirus Antibodies Ratio at EOT | Baseline: Type I | 0.02447 ratio | Standard Deviation 0.027568 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline Poliovirus Antibodies Ratio at EOT | EOT: Type I | 0.00913 ratio | Standard Deviation 0.024223 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline Poliovirus Antibodies Ratio at EOT | Baseline: Type III | 0.03641 ratio | Standard Deviation 0.036709 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline Poliovirus Antibodies Ratio at EOT | EOT: Type III | 0.01141 ratio | Standard Deviation 0.029889 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline Poliovirus Antibodies Ratio at EOT | EOT: Type III | 0.01013 ratio | Standard Deviation 0.028461 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline Poliovirus Antibodies Ratio at EOT | Baseline: Type I | 0.02373 ratio | Standard Deviation 0.028092 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline Poliovirus Antibodies Ratio at EOT | Baseline: Type III | 0.03432 ratio | Standard Deviation 0.036653 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline Poliovirus Antibodies Ratio at EOT | EOT: Type I | 0.00845 ratio | Standard Deviation 0.023091 |
Secondary
Phase 2: Immune Reconstitution-Change From Baseline Total Immunoglobulin at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Baseline, EOT [Month 7]
Population: Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the number of participants with data available for analyses. Number analyzed= number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline Total Immunoglobulin at EOT | Baseline | 2086.6 mg/dl | Standard Deviation 615.62 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Immune Reconstitution-Change From Baseline Total Immunoglobulin at EOT | Change from Baseline at EOT | -582.3 mg/dl | Standard Deviation 565.52 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline Total Immunoglobulin at EOT | Baseline | 2045.1 mg/dl | Standard Deviation 583.04 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Immune Reconstitution-Change From Baseline Total Immunoglobulin at EOT | Change from Baseline at EOT | -556.3 mg/dl | Standard Deviation 553.97 |
Secondary
Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Cycle 1-3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 1 Day 1 | 51.6 day*µg/mL | Standard Deviation 17.17 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 1 Day 15 | 45.6 day*µg/mL | Standard Deviation 38.87 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 3 Day 1 | 53.7 day*µg/mL | Standard Deviation 10.16 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 3 Day 15 | 57.2 day*µg/mL | Standard Deviation 12.37 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 1 Day 1 | 49.6 day*µg/mL | Standard Deviation 17.41 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 1 Day 15 | 55.8 day*µg/mL | Standard Deviation 20.77 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 3 Day 1 | 63.0 day*µg/mL | Standard Deviation 17.1 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 3 Day 15 | 60.9 day*µg/mL | Standard Deviation 11.23 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 3 Day 15 | 61.7 day*µg/mL | Standard Deviation 11.81 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 1 Day 1 | 49.3 day*µg/mL | Standard Deviation 14.75 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 1 Day 1 | 48.8 day*µg/mL | Standard Deviation 16.58 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 1 Day 15 | 46.7 day*µg/mL | Standard Deviation 31.81 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 3 Day 1 | 64.4 day*µg/mL | Standard Deviation 18.99 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 3 Day 1 | 54.6 day*µg/mL | Standard Deviation 7.38 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 1 Day 15 | 54.8 day*µg/mL | Standard Deviation 19.52 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 3 Day 15 | 59.1 day*µg/mL | Standard Deviation 9.38 |
Secondary
Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Cycle 1-3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 1 Day 1 | 27.8 µg/mL | Standard Deviation 8.56 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 1 Day 15 | 23.3 µg/mL | Standard Deviation 6.88 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 3 Day 1 | 22.0 µg/mL | Standard Deviation 2.92 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 3 Day 15 | 25.6 µg/mL | Standard Deviation 7.93 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 1 Day 1 | 22.8 µg/mL | Standard Deviation 5.29 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 1 Day 15 | 25.4 µg/mL | Standard Deviation 5.02 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 3 Day 1 | 27.7 µg/mL | Standard Deviation 6.14 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 3 Day 15 | 25.4 µg/mL | Standard Deviation 3.85 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 3 Day 15 | 26.0 µg/mL | Standard Deviation 4.76 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 1 Day 1 | 26.7 µg/mL | Standard Deviation 7.34 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 1 Day 1 | 22.7 µg/mL | Standard Deviation 5 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 1 Day 15 | 22.7 µg/mL | Standard Deviation 5.72 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 3 Day 1 | 27.6 µg/mL | Standard Deviation 5.84 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 3 Day 1 | 22.4 µg/mL | Standard Deviation 2.15 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Negative: Cycle 1 Day 15 | 25.2 µg/mL | Standard Deviation 4.91 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ATA Positive: Cycle 3 Day 15 | 24.2 µg/mL | Standard Deviation 6.07 |
Secondary
Phase 2: Mean Plasma AUC0-15 of MMAE
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Plasma AUC0-15 of MMAE | Cycle 1 Day 1 | 31.2 day*ng/mL | Standard Deviation 16.2 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Plasma AUC0-15 of MMAE | Cycle 1 Day 15 | 18.4 day*ng/mL | Standard Deviation 11.9 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Plasma AUC0-15 of MMAE | Cycle 3 Day 1 | 11.5 day*ng/mL | Standard Deviation 5.16 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Plasma AUC0-15 of MMAE | Cycle 3 Day 15 | 12.3 day*ng/mL | Standard Deviation 6.12 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Plasma AUC0-15 of MMAE | Cycle 3 Day 15 | 11.3 day*ng/mL | Standard Deviation 5.9 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Plasma AUC0-15 of MMAE | Cycle 1 Day 1 | 31.0 day*ng/mL | Standard Deviation 16.8 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Plasma AUC0-15 of MMAE | Cycle 3 Day 1 | 11.1 day*ng/mL | Standard Deviation 4.93 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Plasma AUC0-15 of MMAE | Cycle 1 Day 15 | 17.9 day*ng/mL | Standard Deviation 11.4 |
Secondary
Phase 2: Mean Plasma Cmax of MMAE
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Plasma Cmax of MMAE | Cycle 3 Day 1 | 1.75 ng/mL | Standard Deviation 0.643 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Plasma Cmax of MMAE | Cycle 1 Day 15 | 2.95 ng/mL | Standard Deviation 1.66 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Plasma Cmax of MMAE | Cycle 1 Day 1 | 5.49 ng/mL | Standard Deviation 2.62 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Plasma Cmax of MMAE | Cycle 3 Day 15 | 1.74 ng/mL | Standard Deviation 0.599 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Plasma Cmax of MMAE | Cycle 3 Day 15 | 1.61 ng/mL | Standard Deviation 0.597 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Plasma Cmax of MMAE | Cycle 3 Day 1 | 1.69 ng/mL | Standard Deviation 0.635 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Plasma Cmax of MMAE | Cycle 1 Day 1 | 5.49 ng/mL | Standard Deviation 2.8 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Plasma Cmax of MMAE | Cycle 1 Day 15 | 2.81 ng/mL | Standard Deviation 1.57 |
Secondary
Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of Brentuximab Vedotin at Cycle 1 Day 1 | 49.7 day*µg/mL | Standard Deviation 17.2 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of Brentuximab Vedotin at Cycle 1 Day 15 | 54.9 day*µg/mL | Standard Deviation 22.2 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of Brentuximab Vedotin at Cycle 3 Day 1 | 62.6 day*µg/mL | Standard Deviation 16.9 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of Brentuximab Vedotin at Cycle 3 Day 15 | 60.6 day*µg/mL | Standard Deviation 11.1 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of TAb at Cycle 1 Day 1 | 77.2 day*µg/mL | Standard Deviation 18.6 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of TAb at Cycle 1 Day 15 | 97.3 day*µg/mL | Standard Deviation 28.7 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of TAb at Cycle 3 Day 1 | 119 day*µg/mL | Standard Deviation 30.6 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of TAb at Cycle 3 Day 15 | 124 day*µg/mL | Standard Deviation 21.6 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of TAb at Cycle 3 Day 15 | 125 day*µg/mL | Standard Deviation 24.1 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of Brentuximab Vedotin at Cycle 1 Day 1 | 48.8 day*µg/mL | Standard Deviation 16.3 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of TAb at Cycle 1 Day 1 | 77.6 day*µg/mL | Standard Deviation 18 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of Brentuximab Vedotin at Cycle 1 Day 15 | 54.0 day*µg/mL | Standard Deviation 20.6 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of TAb at Cycle 3 Day 1 | 120 day*µg/mL | Standard Deviation 29.1 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of Brentuximab Vedotin at Cycle 3 Day 1 | 63.9 day*µg/mL | Standard Deviation 18.6 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of TAb at Cycle 1 Day 15 | 98.1 day*µg/mL | Standard Deviation 27 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb | AUC0-15d of Brentuximab Vedotin at Cycle 3 Day 15 | 61.4 day*µg/mL | Standard Deviation 11.5 |
Secondary
Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of TAb Vedotin at Cycle 1 Day 15 | 26.5 µg/mL | Standard Deviation 9.02 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of TAb Vedotin at Cycle 3 Day 1 | 29.5 µg/mL | Standard Deviation 8.89 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of TAb Vedotin at Cycle 3 Day 15 | 32.2 µg/mL | Standard Deviation 11 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of Brentuximab Vedotin at Cycle 1 Day 1 | 23.1 µg/mL | Standard Deviation 5.54 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of Brentuximab Vedotin at Cycle 1 Day 15 | 25.3 µg/mL | Standard Deviation 5.12 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of Brentuximab Vedotin at Cycle 3 Day 1 | 27.4 µg/mL | Standard Deviation 6.14 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of Brentuximab Vedotin at Cycle 3 Day 15 | 25.4 µg/mL | Standard Deviation 4.03 |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of TAb Vedotin at Cycle 1 Day 1 | 22.1 µg/mL | Standard Deviation 5.34 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of TAb Vedotin at Cycle 1 Day 1 | 22.4 µg/mL | Standard Deviation 5.23 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of TAb Vedotin at Cycle 1 Day 15 | 26.4 µg/mL | Standard Deviation 8.52 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of Brentuximab Vedotin at Cycle 1 Day 15 | 24.9 µg/mL | Standard Deviation 4.97 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of TAb Vedotin at Cycle 3 Day 1 | 29.5 µg/mL | Standard Deviation 8.44 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of Brentuximab Vedotin at Cycle 3 Day 15 | 25.8 µg/mL | Standard Deviation 4.81 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of TAb Vedotin at Cycle 3 Day 15 | 31.4 µg/mL | Standard Deviation 10.4 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of Brentuximab Vedotin at Cycle 3 Day 1 | 27.3 µg/mL | Standard Deviation 5.82 |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb | Cmax of Brentuximab Vedotin at Cycle 1 Day 1 | 23.0 µg/mL | Standard Deviation 5.21 |
Secondary
Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of Brentuximab Vedotin at Cycle 1 Day 1 | 1.03 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of Brentuximab Vedotin at Cycle 1 Day 15 | 1.00 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of Brentuximab Vedotin at Cycle 3 Day 1 | 1.00 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of Brentuximab Vedotin at Cycle 3 Day 15 | 1.00 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of TAb at Cycle 1 Day 1 | 1.01 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of TAb at Cycle 1 Day 15 | 1.00 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of TAb at Cycle 3 Day 1 | 1.00 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of TAb at Cycle 3 Day 15 | 1.00 hour |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of TAb at Cycle 3 Day 15 | 1.00 hour |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of Brentuximab Vedotin at Cycle 1 Day 1 | 1.00 hour |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of TAb at Cycle 1 Day 1 | 1.00 hour |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of Brentuximab Vedotin at Cycle 1 Day 15 | 1.00 hour |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of TAb at Cycle 3 Day 1 | 1.00 hour |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of Brentuximab Vedotin at Cycle 3 Day 1 | 1.00 hour |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of TAb at Cycle 1 Day 15 | 1.00 hour |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum | Tmax of Brentuximab Vedotin at Cycle 3 Day 15 | 1.00 hour |
Secondary
Phase 2: Median Tmax of MMAE in Plasma
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Population: The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. Number analyzed is number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Median Tmax of MMAE in Plasma | Cycle 1 Day 1 | 44.1 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Median Tmax of MMAE in Plasma | Cycle 1 Day 15 | 42.9 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Median Tmax of MMAE in Plasma | Cycle 3 Day 1 | 44.9 hour |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Median Tmax of MMAE in Plasma | Cycle 3 Day 15 | 45.4 hour |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Median Tmax of MMAE in Plasma | Cycle 3 Day 15 | 46.0 hour |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Median Tmax of MMAE in Plasma | Cycle 1 Day 1 | 44.4 hour |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Median Tmax of MMAE in Plasma | Cycle 3 Day 1 | 45.3 hour |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Median Tmax of MMAE in Plasma | Cycle 1 Day 15 | 42.9 hour |
Secondary
Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Up to 24 months
Population: The Safety Population included participants who received at least 1 dose of any drug in the A+AVD regimen. Data is reported as per ATA positive and negative status.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs | ATA Negative: AEs | 48 Participants |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs | ATA Positive: AEs | 3 Participants |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs | ATA Negative: SAEs | 21 Participants |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs | ATA Positive: SAEs | 2 Participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs | ATA Positive: SAEs | 3 Participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs | ATA Negative: AEs | 55 Participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs | ATA Negative: SAEs | 21 Participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs | ATA Positive: AEs | 4 Participants |
Secondary
Phase 2: Overall Survival (OS)
Overall survival was defined as time from first dose until death. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive, including study closure. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Up to 24 months
Population: The safety/efficacy population included participants who received at least 1 dose of any drug in the A+AVD regimen.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Overall Survival (OS) | NA months |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Overall Survival (OS) | NA months |
Secondary
Phase 2: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants
CR is defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Up to 24 months
Population: Immunogenicity Population included participants who received at least 1 dose of study drug and had the baseline immunogenicity sample and at least 1 postbaseline immunogenicity sample assessment. Number analyzed is the number of participants analyzed for the specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants | ATA Negative | 75 percentage of participants |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants | Transiently ATA Positive | 67 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants | ATA Negative | 76 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants | Transiently ATA Positive | 75 percentage of participants |
Secondary
Phase 2: Percentage of Participants Receiving Irradiation for HL Following Study Treatment
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Up to 24 months
Population: The safety/efficacy population included participants who received at least 1 dose of any drug in the A+AVD regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants Receiving Irradiation for HL Following Study Treatment | 25 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants Receiving Irradiation for HL Following Study Treatment | 24 percentage of participants |
Secondary
Phase 2: Percentage of Participants Who Experienced AEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
Population: The safety population included participants who had received at least 1 dose of any study drug (A+AVD regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants Who Experienced AEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy | 100 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants Who Experienced AEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy | 100 percentage of participants |
Secondary
Phase 2: Percentage of Participants Who Experienced Peripheral Neuropathy, Regardless of Seriousness, From the First Dose of Protocol Therapy
Peripheral Neuropathy (PN) was defined by the peripheral neuropathy standardized MedDRA query (SMQ) broad search. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Up to 24 months
Population: The safety population included participants who received at least 1 dose of any drug in the A+AVD regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants Who Experienced Peripheral Neuropathy, Regardless of Seriousness, From the First Dose of Protocol Therapy | 20 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants Who Experienced Peripheral Neuropathy, Regardless of Seriousness, From the First Dose of Protocol Therapy | 19 percentage of participants |
Secondary
Phase 2: Percentage of Participants Who Experienced SAEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
Population: The safety population included participants who had received at least 1 dose of any study drug (A+AVD regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants Who Experienced SAEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy | 45 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants Who Experienced SAEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy | 41 percentage of participants |
Secondary
Phase 2: Percentage of Participants Who Were ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive
ATA positive was defined as participants who have a positive ATA in any postbaseline sample. Transiently ATA positive was defined as participants who have positive ATA in 1 or 2 postbaseline samples. Persistently ATA positive was defined as participants who have positive ATA in more than 2 postbaseline timepoints. Transiently ATA positive was defined as participants who have positive ATA in 1 or 2 postbaseline samples. nATA positive was defined as participants who have at least one positive nATA in any postbaseline ATA positive sample. Here, percentage of participants who were transiently or persistently ATA positive are considered as ATA positive. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: From first dose until 30 days after the last dose of study drug (up to 7 months)
Population: Immunogenicity population included participants who received at least 1 dose of study drug and had the baseline immunogenicity sample and at least 1 postbaseline immunogenicity sample assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants Who Were ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive | Persistently ATA Positive | 0 percentage of participants |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants Who Were ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive | nATA Positive | 4 percentage of participants |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants Who Were ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive | Transiently ATA Positive | 6 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants Who Were ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive | Persistently ATA Positive | 0 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants Who Were ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive | Transiently ATA Positive | 7 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants Who Were ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive | nATA Positive | 3 percentage of participants |
Secondary
Phase 2: Percentage of Participants With Low and High ATA Titer Values
High ATA titer was defined as participants who have at least one postbaseline ATA titer \>25. Low ATA titer was defined as participants whose postbaseline ATA titer are all \<=25. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Up to 6 months
Population: Immunogenicity population included participants who received at least 1 dose of study drug and had the baseline immunogenicity sample and at least 1 postbaseline immunogenicity sample assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants With Low and High ATA Titer Values | ATA Titer Low | 6 percentage of participants |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Percentage of Participants With Low and High ATA Titer Values | ATA Titer High | 0 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants With Low and High ATA Titer Values | ATA Titer Low | 7 percentage of participants |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Percentage of Participants With Low and High ATA Titer Values | ATA Titer High | 0 percentage of participants |
Secondary
Phase 2: Progression-free Survival (PFS)
PFS per IRF:time from first dose until disease progression per IRF/death due to any cause,whichever occurred first.Participants with no objective progressive disease (PD),did not die,were still on study follow-up at time of analysis were removed from study prior to documentation of PD,PFS was censored on date of last adequate disease assessment before initiation of any non-protocol,alternative therapy.Participants who were on antitumor treatment,other than SCT/radiotherapy,censoring was at last adequate disease assessment before initiation of such alternative treatment.If participant experienced disease progression per IRF/died after initiation of antitumor treatment,other than SCT/radiotherapy,such participant was censored and not considered having PFS.Outcome measure was planned to be assessed for all participant treated at recommended dose in Phase 2.As per SAP,Phase 2 data was summarized and reported in two arms:Phase 2 and Phase 1 + Phase 2.
Time frame: Up to 24 months
Population: The safety/efficacy population included participants who received at least 1 dose of any drug in the A+AVD regimen.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Progression-free Survival (PFS) | NA months |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Progression-free Survival (PFS) | NA months |
Secondary
Phase 2: Time to Onset and Resolution for All Peripheral Neuropathy Events
Time to onset of first event was defined as time from first dose of study drug to onset of first treatment-emergent PN event. Time to resolution was calculated as the time from onset date to the date of resolution PN (SMQ) event. Participants with multiple resolved events were counted once at the longest time to resolution. Resolution was defined as an event outcome of resolved or resolved with sequelae. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Time frame: Up to 24 months
Population: The safety population included participants who received at least 1 dose of any drug in the A+AVD regimen. Overall number analyzed signifies participants who had peripheral neuropathy were analyzed for this outcome measure, number analyzed are participants with evaluable for the specific category.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Time to Onset and Resolution for All Peripheral Neuropathy Events | Time to Onset | 5.93 weeks |
| Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD | Phase 2: Time to Onset and Resolution for All Peripheral Neuropathy Events | Time to Resolution | 1.57 weeks |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Time to Onset and Resolution for All Peripheral Neuropathy Events | Time to Onset | 5.93 weeks |
| Phase 1 + Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Phase 2: Time to Onset and Resolution for All Peripheral Neuropathy Events | Time to Resolution | 1.57 weeks |