Hodgkin Disease, Lymphoma, Large-Cell, Anaplastic
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics (PK) of brentuximab vedotin as a single agent in Chinese participants with relapsed/refractory CD30+ Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL).
Detailed description
The drug being tested in this study is called brentuximab vedotin. This study will look at efficacy, safety and PK of brentuximab vedotin in Chinese participants with relapsed/refractory CD30+ HL or sALCL. The study will enroll approximately 30 patients. Participants will receive: • Brentuximab vedotin 1.8 mg/kg All participants will be administered IV infusion on Day 1 each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles. This multi-center trial will be conducted in China only. The overall time to participate in this study is 3.5 years. Participants will make multiple visits to the clinic, and will be followed for overall survival (OS) every 12 weeks until death, withdrawal of consent, 18 months after end of treatment (EOT) or study closure, whichever occurs first.
Interventions
DRUGBrentuximab Vedotin
Brentuximab vedotin IV infusion
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Have histologically confirmed CD30+ hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (sALCL). Immunohistochemistry or flow cytometry may be performed on either original diagnostic biopsy material or biopsy of relapsed disease, and pathology reports of CD30+ or their copies should be retained at the site. 2. With CD30+ HL or sALCL who have relapsed from or are refractory to previous treatments. 3. Fluorodeoxyglucose (FDG)- positron emission tomography (PET) positive and measurable disease of at least 1.5 cm in the longest diameter by computed tomography (CT), as assessed by the site. 4. Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) sampling. 6. Must have the following required screening laboratory data. Participants must not have received recombinant granulocyte-colony stimulating factor (G-CSF) or platelet transfusion within 1 week before the screening hematology assessment. 1. Absolute neutrophil count ≥1500/μL. 2. Platelet count ≥75,000/μL. 3. Serum bilirubin level ≤1.5 times the upper limit of the normal range (ULN). 4. Serum creatinine level ≤1.5 times the ULN. 5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the ULN. 7. Survival for 3 or more months must be expected.
Exclusion criteria
1. With current diagnosis of primary cutaneous anaplastic large cell lymphoma (ALCL) (participants with other organ involvement who have transformed to sALCL are eligible). 2. With any active viral, bacterial, or fungal infection within 2 weeks before the first dose of brentuximab vedotin. 3. With cardiac failure categorized as Class III or IV according to the New York Heart Association criteria, uncontrolled coronary artery disease or uncontrolled arrhythmia despite of appropriate medical therapy, or a history of myocardial infarction within 6 months before the first dose of brentuximab vedotin. 4. With uncontrolled diabetes mellitus. 5. Peripheral neuropathy ≥Grade 2. 6. With a history of another malignancy that has not been in remission for at least 3 years. The following are exempt from the 3-year limit: 1. Nonmelanoma skin cancer. 2. Curatively treated localized prostate cancer. 3. Cervical carcinoma in situ. 7. With known cerebral/meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML). 8. With a positive result in the screening test for human immunodeficiency virus (HIV) antibody. 9. Known hepatitis B virus (HBV) surface antigen seropositive or positive hepatitis C virus (HCV) antibody. Note: participants who have positive HBV core antibody can be enrolled but must have an undetectable HBV viral load. 10. With a history of liver fibrosis or cirrhosis and clinical signs and symptoms indicating liver fibrosis or cirrhosis. 11. Have received autologous stem cell transplantation (auto-SCT) within 12 weeks before the first dose of brentuximab vedotin. 12. With history of allogeneic stem cell transplantation (allo-SCT). 13. Have received treatment for malignancies (including radiation, chemotherapy, and hormone therapy) within 4 weeks before the first dose of brentuximab vedotin and participants who have received treatment for malignancies with biologics (including molecular target drug) or radioisotopic therapy within 12 weeks before the first dose of brentuximab vedotin. 14. Have unresolved toxicity higher than Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 4.03) attributed to any prior therapy/procedure (excluding alopecia or non-clinically significant and asymptomatic laboratory abnormalities). 15. Have received systemic corticosteroids at doses greater than the equivalent of 20 mg/day of prednisone within 1 week before the first dose of brentuximab vedotin. 16. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of the safety and toxicity of the prescribed regimens.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment until disease progression death or end of treatment (approximately 12 months) | ORR is defined as the percentage of participants who have achieved complete remission (CR)=disappearance of all evidence of disease or partial remission (PR)=regression of greater than or equal to 50% of measurable disease and no new site by end of treatment (EOT) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | First dose of study drug up to 30 days after last dose of study drug (approximately 12 months) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs or worsens after receiving study drug. |
| Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | First dose of study drug up to 30 days after last dose of study drug (approximately 12 months) | Clinical Laboratory tests included tests of Chemistry, Hematology and Urinalysis prespecified in the protocol. Abnormal laboratory values assessed by the investigator that lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or were considered by the investigator to be clinically significant changes from Baseline were recorded as Adverse Events. Neutropenia (pooled) includes preferred terms Neutropenia and Neutrophil count decreased. |
| Number of Participants With Abnormal Vital Signs Reported as Adverse Events | First dose of study drug up to 30 days after last dose of study drug (approximately 12 months) | Vital signs included blood pressure in the sitting position, pulse rate, axillary temperature and weight. Abnormal vital sign values considered by the investigator to be clinically significant were recorded as Adverse Events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| B Symptom Resolution Rate | Day 1 of each cycle (each cycle was of 3 weeks) up to 30 days after last dose of study drug (approximately 12 months) | B Symptom Resolution Rate is defined as the percentage of participants with lymphoma-related symptoms (B symptoms: fever, night sweats, or weight loss \>10%) at baseline who achieved resolution of all B symptoms at any time during the treatment period. |
| Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) | Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb) | Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE) | Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Brentuximab Vedotin ADC | Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Complete Remission (CR) Rate | Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment, and every 12 weeks during PFS follow-up period, until disease progression death or end of treatment (approximately 12 months) | CR rate is defined as the percentage of participants who have achieved CR by EOT. CR is defined as disappearance of all evidence of disease per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE | Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| AUC(0-∞): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC | Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| AUC(0-∞): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for TAb | Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| AUC(0-∞): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MMAE | Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment until disease progression, death or end of treatment (approximately 12 months) | Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA development) using a laboratory test to determine ATA titers. Confirmed ATA-positive response was categorized as transient (defined as 1 or 2 post-baseline confirmed ATA-positive responses) and persistent (defined as more than 2 post-baseline confirmed ATA positive responses) and by nATA status. The number of participants in each baseline ATA and post-baseline ATA categories are reported. |
| Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb | Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Duration of Response (DOR) | Up to 3.2 years | DOR is defined as the time between the first documentation of objective tumor response (CR or PR) and the first subsequent documentation of objective tumor progression or death due to any cause, whichever occurs first. CR is defined as disappearance of all evidence of disease. PR is defined as regression of greater than or equal to 50% of measurable disease and no new sites. |
| Progression Free Survival (PFS) | Up to 3.2 years | PFS is defined as the time from the start of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. |
| Overall Survival (OS) | Up to 3.2 years | Overall survival is defined as the time from the start of treatment to the date of death. |
Countries
China
Participant flow
Recruitment details
Participants took part in the study at 7 investigative sites in China. The study was conducted from 07 November 2016 to 3 February 2020.
Pre-assignment details
Participants with a diagnosis of Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL) were enrolled to receive brentuximab vedotin 1.8 mg/kg, intravenous (IV) infusion, Day 1 of every 3-week cycle.
Participants by arm
| Arm | Count |
|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL). | 30 |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory Systemic Anaplastic Large Cell Lymphoma (sALCL). | 9 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 4 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) | Total |
|---|---|---|---|
| Age, Continuous | 31.9 years STANDARD_DEVIATION 8.91 | 41.1 years STANDARD_DEVIATION 15.28 | 34.0 years STANDARD_DEVIATION 11.19 |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 30 Participants | 9 Participants | 39 Participants |
| Race/Ethnicity, Customized Race Asian | 30 Participants | 9 Participants | 39 Participants |
| Region of Enrollment China | 30 Participants | 9 Participants | 39 Participants |
| Sex: Female, Male Female | 13 Participants | 2 Participants | 15 Participants |
| Sex: Female, Male Male | 17 Participants | 7 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 30 | 3 / 9 |
| other Total, other adverse events | 30 / 30 | 9 / 9 |
| serious Total, serious adverse events | 1 / 30 | 1 / 9 |
Outcome results
Primary
Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events
Clinical Laboratory tests included tests of Chemistry, Hematology and Urinalysis prespecified in the protocol. Abnormal laboratory values assessed by the investigator that lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or were considered by the investigator to be clinically significant changes from Baseline were recorded as Adverse Events. Neutropenia (pooled) includes preferred terms Neutropenia and Neutrophil count decreased.
Time frame: First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)
Population: Safety Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Neutrophil count increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Aspartate aminotransferase increased | 17 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Gamma-glutamyltransferase increased | 3 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood bilirubin increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Reticulocyte count decreased | 9 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Reticulocyte count increased | 6 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Haemoglobin decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Reticulocyte percentage increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | White blood cell count decreased | 4 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Lymphocyte count decreased | 5 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Lymphocyte percentage decreased | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Lymphocyte count increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Lymphocyte percentage increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Monocyte count increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Alanine aminotransferase increased | 18 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Neutrophil percentage decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | White blood cell count increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Platelet count decreased | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood uric acid increased | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood glucose increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood albumin decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Protein total decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood creatinine increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood urea decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood urea increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood lactate dehydrogenase increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood alkaline phosphatase increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood cholesterol increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood calcium decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood calcium increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood chloride decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood phosphorus decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood potassium decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood triglycerides increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Glucose urine present | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Leukopenia | 15 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Anaemia | 12 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hyperuricaemia | 4 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hypertriglyceridaemia | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hypokalaemia | 3 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood creatine phosphokinase increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Total bile acids increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Alpha hydroxybutyrate dehydrogenase increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood magnesium decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | High density lipoprotein decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hypercalcaemia | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hyperglycaemia | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hypoalbuminaemia | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hypocalcaemia | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hyponatraemia | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Lipoprotein (a) increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Low density lipoprotein increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Monocytosis | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Red blood cell sedimentation rate increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Thrombocytopenia | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Neutropenia (Pooled) | 19 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Monocytosis | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Alanine aminotransferase increased | 6 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood calcium decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Aspartate aminotransferase increased | 6 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Alpha hydroxybutyrate dehydrogenase increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Gamma-glutamyltransferase increased | 4 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood calcium increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood bilirubin increased | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hyponatraemia | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Reticulocyte count decreased | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood chloride decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Reticulocyte count increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood magnesium decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Haemoglobin decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood phosphorus decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Reticulocyte percentage increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Thrombocytopenia | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | White blood cell count decreased | 3 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood potassium decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Lymphocyte count decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | High density lipoprotein decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Lymphocyte percentage decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood triglycerides increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Lymphocyte count increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Lipoprotein (a) increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Lymphocyte percentage increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Glucose urine present | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Monocyte count increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hypercalcaemia | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Neutrophil count increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Leukopenia | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Neutrophil percentage decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Red blood cell sedimentation rate increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | White blood cell count increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Anaemia | 3 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Platelet count decreased | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hyperglycaemia | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood uric acid increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hyperuricaemia | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood glucose increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Low density lipoprotein increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood albumin decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hypertriglyceridaemia | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Protein total decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hypoalbuminaemia | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood creatinine increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hypokalaemia | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood urea decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Neutropenia (Pooled) | 5 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood urea increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood creatine phosphokinase increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood lactate dehydrogenase increased | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Hypocalcaemia | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood alkaline phosphatase increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Total bile acids increased | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events | Blood cholesterol increased | 1 Participants |
Primary
Number of Participants With Abnormal Vital Signs Reported as Adverse Events
Vital signs included blood pressure in the sitting position, pulse rate, axillary temperature and weight. Abnormal vital sign values considered by the investigator to be clinically significant were recorded as Adverse Events.
Time frame: First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)
Population: Safety Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Weight increased | 4 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Weight decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Weight increased | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Weight decreased | 2 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs or worsens after receiving study drug.
Time frame: First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)
Population: Safety Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 30 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 9 Participants |
Primary
Overall Response Rate (ORR)
ORR is defined as the percentage of participants who have achieved complete remission (CR)=disappearance of all evidence of disease or partial remission (PR)=regression of greater than or equal to 50% of measurable disease and no new site by end of treatment (EOT) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time frame: Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment until disease progression death or end of treatment (approximately 12 months)
Population: Modified Intent-to-Treat (mITT) Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Overall Response Rate (ORR) | 70.0 percentage of participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Overall Response Rate (ORR) | 66.7 percentage of participants |
Secondary
AUC(0-∞): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MMAE
Time frame: Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: PK-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | AUC(0-∞): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MMAE | 36.8625 day*ug/mL | Standard Deviation 22.79816 |
Secondary
AUC(0-∞): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC
Time frame: Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: Participants from the PK-evaluable Populations, participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist, with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | AUC(0-∞): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC | 79.9951 day*ug/mL | Standard Deviation 19.59116 |
Secondary
AUC(0-∞): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for TAb
Time frame: Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: PK-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | AUC(0-∞): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for TAb | 168.6618 day*ug/mL | Standard Deviation 41.6284 |
Secondary
B Symptom Resolution Rate
B Symptom Resolution Rate is defined as the percentage of participants with lymphoma-related symptoms (B symptoms: fever, night sweats, or weight loss \>10%) at baseline who achieved resolution of all B symptoms at any time during the treatment period.
Time frame: Day 1 of each cycle (each cycle was of 3 weeks) up to 30 days after last dose of study drug (approximately 12 months)
Population: Participants from the mITT Population, all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin, who had lymphoma-related B symptoms at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | B Symptom Resolution Rate | 50.0 percentage of participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | B Symptom Resolution Rate | 100.00 percentage of participants |
Secondary
Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE)
Time frame: Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: PK-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE) | Cycle 1 | 5.1623 ug/mL | Standard Deviation 3.69893 |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE) | Cycle 2 | 3.6218 ug/mL | Standard Deviation 2.89331 |
Secondary
Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC)
Time frame: Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: Pharmacokinetic (PK)-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) | Cycle 1 | 36.9504 micrograms/milliliter (ug/mL) | Standard Deviation 9.9036 |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) | Cycle 2 | 32.4341 micrograms/milliliter (ug/mL) | Standard Deviation 5.83197 |
Secondary
Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb)
Time frame: Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: PK-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb) | Cycle 1 | 38.2293 ug/mL | Standard Deviation 7.95483 |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb) | Cycle 2 | 39.9859 ug/mL | Standard Deviation 12.43445 |
Secondary
Complete Remission (CR) Rate
CR rate is defined as the percentage of participants who have achieved CR by EOT. CR is defined as disappearance of all evidence of disease per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time frame: Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment, and every 12 weeks during PFS follow-up period, until disease progression death or end of treatment (approximately 12 months)
Population: mITT Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Complete Remission (CR) Rate | 20.0 percentage of participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Complete Remission (CR) Rate | 55.6 percentage of participants |
Secondary
Duration of Response (DOR)
DOR is defined as the time between the first documentation of objective tumor response (CR or PR) and the first subsequent documentation of objective tumor progression or death due to any cause, whichever occurs first. CR is defined as disappearance of all evidence of disease. PR is defined as regression of greater than or equal to 50% of measurable disease and no new sites.
Time frame: Up to 3.2 years
Population: mITT Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin. Only responders were analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Duration of Response (DOR) | 12.0 months |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Duration of Response (DOR) | NA months |
Secondary
Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin
Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA development) using a laboratory test to determine ATA titers. Confirmed ATA-positive response was categorized as transient (defined as 1 or 2 post-baseline confirmed ATA-positive responses) and persistent (defined as more than 2 post-baseline confirmed ATA positive responses) and by nATA status. The number of participants in each baseline ATA and post-baseline ATA categories are reported.
Time frame: Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment until disease progression, death or end of treatment (approximately 12 months)
Population: Immunogenicity Population included participants who received at least 1 dose of brentuximab vedotin and had ATA status assessment at baseline, and at least 1 postbaseline sample. Number analyzed is the number of participants with data available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Negative | 29 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Negative, nATA Positive | 8 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Positive | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Positive, ATA Negative | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Positive, Transiently ATA Positive | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Positive, Persistently ATA Positive | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Positive, nATA Negative | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Positive, nATA Positive | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Negative, ATA Negative | 21 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Negative, Transiently ATA Positive | 7 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Negative, Persistently ATA Positive | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Negative, nATA Negative | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Negative | 9 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Negative, nATA Positive | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Negative, ATA Negative | 8 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Negative, nATA Negative | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Negative, Transiently ATA Positive | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Positive | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin | Baseline ATA Negative, Persistently ATA Positive | 0 Participants |
Secondary
Overall Survival (OS)
Overall survival is defined as the time from the start of treatment to the date of death.
Time frame: Up to 3.2 years
Population: mITT Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Overall Survival (OS) | NA months |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Overall Survival (OS) | NA months |
Secondary
Progression Free Survival (PFS)
PFS is defined as the time from the start of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
Time frame: Up to 3.2 years
Population: mITT Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Progression Free Survival (PFS) | 13.5 months |
| Brentuximab Vedotin 1.8 mg/kg (sALCL) | Progression Free Survival (PFS) | 23.2 months |
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Brentuximab Vedotin ADC
Time frame: Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: PK-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Brentuximab Vedotin ADC | Cycle 1 | 0.0576 days |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Brentuximab Vedotin ADC | Cycle 2 | 0.0528 days |
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE
Time frame: Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: PK-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE | Cycle 1 | 2.0729 days |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE | Cycle 2 | 2.9785 days |
Secondary
Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb
Time frame: Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: PK-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg (HL) | Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb | Cycle 1 | 0.0653 days |
| Brentuximab Vedotin 1.8 mg/kg (HL) | Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb | Cycle 2 | 0.0660 days |