Hodgkin Lymphoma
Conditions
Keywords
Brentuximab vedotin, Doxorubicin, Vinblastine, Dacarbazine, Nivolumab, Seattle Genetics
Brief summary
This trial will study two treatment combinations for classical Hodgkin lymphoma (cHL). This trial will find out if these two treatment combinations work to treat cHL. It will also find out what side effects occur. A side effect is anything the drug does besides treating cancer. This study will have three parts (Parts A, B, and C). The drugs used in Part A are a combination of targeted anticancer drug (brentuximab vedotin) and three chemotherapy drugs (doxorubicin, vinblastine, and dacarbazine). These four drugs are called A+AVD. Participants will be treated with granulocyte colony stimulating factor (G-CSF) following every dose of A+AVD for 6 cycles of treatment (12 doses). Part A will look at whether the A+AVD drug combination reduces the number of participants who experience the side effect of febrile neutropenia. Febrile neutropenia is a very low white blood cell count and a fever, which can be life threatening. Parts B and C will use drug combination of brentuximab vedotin, plus nivolumab, doxorubicin, and dacarbazine. These four drugs are called AN+AD. Parts B and C will study how well the drugs work to treat cHL and what side effects they cause.
Detailed description
This study will have three parts. Part A of the study is designed to evaluate the incidence of febrile neutropenia, efficacy, and dose intensity in participants with advanced stage classical Hodgkin lymphoma (cHL) receiving granulocyte colony stimulating factor primary prophylaxis (G-PP) administration during treatment with frontline A+AVD. In Part A, participants will be treated with granulocyte colony stimulating factor (G-CSF) following every dose of A+AVD for 6 cycles of treatment. Participants will be treated using institutional standard of care practices for the majority of treatment decisions. Part B is designed to evaluate the combination of brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine (AN+AD) as frontline treatment in participants with advanced cHL. In Part B, participants will be given AN+AD combination for 6 cycles of treatment. This part of the trial will look at whether this combination of drugs is effective and tolerable in participants with Stage II with bulky mediastinal disease and Stage III or IV cHL. Part C is designed to evaluate AN+AD as frontline treatment in participants with early stage cHL. In Part C, participants will be given AN+AD combination for 4 cycles of treatment. This part of the trial will look at whether this combination of drugs is effective and tolerable in participants with Stage I or II cHL with non-bulky mediastinal disease.
Interventions
DRUGbrentuximab vedotin
1.2 mg/kg by IV infusion
DRUGdoxorubicin
25 mg/m\^2 by IV infusion
DRUGvinblastine
6 mg/m\^2 by IV infusion
DRUGdacarbazine
375 mg/m\^2 by IV infusion
DRUGG-CSF
Granulocyte colony stimulating factor (G-CSF) primary prophylaxis administered 24-36 hours after each dose of A+AVD
DRUGnivolumab
240 mg by IV infusion
Sponsors
Bristol-Myers Squibb
Seagen Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Treatment-naïve, classic Hodgkin lymphoma (cHL) participants * Participants enrolling in Part A of the study must have Ann Arbor Stage III or IV disease * Participants enrolling in Part B of the study must have Ann Arbor Stage I or II cH: with bulky mediastinal disease, or Stage III or IV * Participants enrolling in Part C of the study must have Ann Arbor Stage I or II cHL without bulky disease * Histologically confirmed cHL according to the current World Health Organization (WHO) Classification * Bidimensional measurable disease as documented by PET/CT or CT imaging * Age 12 years or older in the United States. For regions outside of the US, participants must 18 years or older. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Exclusion criteria
* Nodular lymphocyte predominant HL * History of another malignancy within 3 years of the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk or metastasis or death. Participants with nonmelanoma skin cancer, localized prostate cancer, or carcinoma in situ of any type are not excluded if they have undergone complete resection * Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy within 4 weeks of the first study drug dose * Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways * Active cerebral/meningeal disease related to the underlying malignancy * Any active Grade 3 or higher viral, bacterial, or fungal infection within two weeks of the first dose of study drug (Grade 3 defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events, NCI CTCAE Version 4.03) * Current therapy with other systemic anti-neoplastic or investigational agents * Planned consolidative radiotherapy (Parts B and C only) * Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity (Parts B and C only) * Grade 3 or higher pulmonary disease unrelated to underlying malignancy * Documented history of idiopathic interstitial pneumonia or diffusing capacity of the lung for carbon monoxide \<50% predicted * History of a cerebral vascular event within 6 months of first dose of study drug * Child-Pugh B or C hepatic impairment * Grade 2 or higher peripheral sensory or motor neuropathy * Participants with acute or chronic graft-versus-host-disease (GvHD) or receiving immunosuppressive therapy as treatment or as prophylaxis against GvHD * Previous treatment with brentuximab vedotin * Participants who are pregnant or breastfeeding * Other serious condition that would impair the participant's ability to receive or tolerate the planned treatment and follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Febrile Neutropenia (FN) Rate (Part A) | 7.5 months | The FN rate is defined as the number of participants who experience treatment-emergent FN. |
| Complete Response (CR) Rate at EOT (Parts B and C) | 7.8 months | CR rate at EOT is defined as the percentage of participants with CR at EOT, according to the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) (Cheson 2016), in participants with previously untreated cHL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (Part A) | 7.2 months | The complete response rate is defined as the percentage of participants with CR at EOT according to the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas (Cheson 2014). |
| Physician-reported Progression Free Survival (PFS) (Part A) | 24 months | The physician-reported PFS rate at 2 years is estimated based on Kaplan-Meier methodology. The determination of antitumor activity will be based on response assessments made according to the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas (Cheson 2014). |
| Number of Participants With Subsequent Anticancer Therapy Utilization (Part A) | 33.8 months | Number of participants with subsequent anticancer therapy have been reported in this outcome measure. |
| Actual Dose Intensity: Brentuximab Vedotin (Part A) | 6.5 months | — |
| Actual Dose Intensity: Doxorubicin, Vinblastine, Dacarbazine (Part A) | 6.5 months | — |
| Relative Dose Intensity (Part A) | 6.5 months | — |
| Rate of Dose Reduction and Delays: Brentuximab Vedotin (Part A) | 6.5 months | — |
| Rate of Dose Reduction and Delays: Doxorubicin (Part A) | 6.5 months | — |
| Rate of Dose Reduction and Delays: Vinblastine (Part A) | 6.5 months | — |
| Number of Participants With Adverse Events of Clinical Interest (AECI) (Part A) | Approximately up to 7.5 months | An adverse event (AE) was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with the treatment. Participants with peripheral neuropathy (PN) adverse events were summarized under AECI. |
| Incidence of Adverse Events (Parts B and C) | 8.9 months | — |
| Incidence of Laboratory Abnormalities (Parts B and C) | 8.9 months | Laboratory values were graded according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.03). As per NCI CTCAE version 4.03 grading, Grade 1 indicated mild or asymptomatic laboratory abnormalities, Grade 2 indicated moderate laboratory abnormalities, and Grade 3 indicated severe and 4 indicated life-threatening laboratory abnormalities. |
| Overall Response Rate (ORR) at EOT (Parts B and C) | Up to 7.8 months | ORR is defined as the percentage of participants with CR or partial response (PR) at EOT according to the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016) in participants with previously untreated cHL. |
| Duration of Response (DOR) at End of Study (Parts B and C) | Up to 51.1 months | DOR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression per the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016) or death, whichever came first. Duration of response was only calculated for the subgroup of participants achieving a CR or PR. Participants without progression or death were censored on the date of the last radiological assessment of measured lesions. Kaplan-Meier method was used. |
| Duration of Complete Response (DOCR) (Parts B and C) | Up to 51.1 months | DOCR was defined as the time from start of the first documentation of CR to the first documentation of tumor progression (per the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016) or death, whichever came first. DOCR was calculated for the subgroup of participants achieving CR. Participants without progression or death were censored on the date of the last radiological assessment of measured lesions. Kaplan-Meier method was used. |
| Event Free Survival (EFS) Rate (Parts B and C) | Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42 | EFS was defined as the time from the start of study treatment to the first documentation of objective tumor progression, death due to any cause, or receipt of subsequent anticancer therapy to treat residual or progressive disease, whichever occurred first. The determination of antitumor activity will be based on objective response assessments made according to Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016). Participants without progression or death were censored on the date of the last radiological assessment of measured lesions. EFS rate was percentage of participants with EFS. |
| PFS Rate (Parts B and C) | At months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42 from the start of study treatment | PFS was defined as the time from start of study treatment to first documentation of objective tumor progression or death. The determination of antitumor activity will be based on objective response assessments made according to Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016). Participants without progression or death were censored on the date of the last radiological assessment of measured lesions. Kaplan-Meier method was used. |
| Overall Survival (OS) Rate (Parts B and C) | At months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42 from the start of study treatment | OS was defined as the time from start of study treatment to date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. Kaplan-Meier method was used. |
| Rate of Dose Reduction and Delays: Dacarbazine (Part A) | 6.5 months | — |
| Primary Refractory Disease Rate (Part A) | 10.2 months | The primary refractory disease rate is defined as the percentage of participants with less than complete response or relapse within 3 months of EOT, according to the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas |
Countries
Australia, Czechia, Italy, Poland, Spain, United States
Participant flow
Pre-assignment details
In this study participant's treatment was completed before primary completion date (PCD), and no treatment was administered after PCD, participants were followed up.
Participants by arm
| Arm | Count |
|---|---|
| Part A A+AVD (brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine) in participants with advanced stage classical Hodgkin lymphoma (cHL). | 41 |
| Part B AN+AD (brentuximab vedotin and nivolumab plus doxorubicin and dacarbazine) in participants with Stage II bulky mediastinal disease and Stage III or IV cHL. | 58 |
| Part C AN+AD (brentuximab vedotin and nivolumab plus doxorubicin and dacarbazine) in participants with Stage I or II cHL with non-bulky mediastinal disease. | 156 |
| Total | 255 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 2 | 1 | 1 |
| Overall Study | Lost to Follow-up | 4 | 10 | 10 |
| Overall Study | Other | 2 | 0 | 2 |
| Overall Study | Study termination by sponsor | 0 | 45 | 139 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 3 |
Baseline characteristics
| Characteristic | Part A | Total | Part C | Part B |
|---|---|---|---|---|
| Age, Continuous | 28 years | 31 years | 31 years | 35 years |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0 | 27 Participants | 185 Participants | 124 Participants | 34 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1 | 13 Participants | 64 Participants | 28 Participants | 23 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 2 | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Missing | 1 Participants | 4 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 36 Participants | 22 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 207 Participants | 127 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 12 Participants | 7 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 8 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 9 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 24 Participants | 17 Participants | 4 Participants |
| Race (NIH/OMB) White | 31 Participants | 212 Participants | 131 Participants | 50 Participants |
| Sex: Female, Male Female | 16 Participants | 129 Participants | 86 Participants | 27 Participants |
| Sex: Female, Male Male | 25 Participants | 126 Participants | 70 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 40 | 1 / 57 | 1 / 154 |
| other Total, other adverse events | 40 / 40 | 57 / 57 | 153 / 154 |
| serious Total, serious adverse events | 19 / 40 | 15 / 57 | 29 / 154 |
Outcome results
Primary
Complete Response (CR) Rate at EOT (Parts B and C)
CR rate at EOT is defined as the percentage of participants with CR at EOT, according to the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) (Cheson 2016), in participants with previously untreated cHL.
Time frame: 7.8 months
Population: For Parts B and C, the full analysis set included all participants who enrolled and received any amount of the combination therapy in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A | Complete Response (CR) Rate at EOT (Parts B and C) | 88 Percentage of participants |
| Part C | Complete Response (CR) Rate at EOT (Parts B and C) | 92 Percentage of participants |
Primary
Febrile Neutropenia (FN) Rate (Part A)
The FN rate is defined as the number of participants who experience treatment-emergent FN.
Time frame: 7.5 months
Population: For Part A, the full analysis set included all participants who received at least 1 dose of A+AVD (any of the study drugs in the regimen).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Febrile Neutropenia (FN) Rate (Part A) | Any treatment-emergent FN | 5 Participants |
| Part A | Febrile Neutropenia (FN) Rate (Part A) | Treatment-related treatment-emergent FN | 5 Participants |
| Part A | Febrile Neutropenia (FN) Rate (Part A) | Grade 3 or higher treatment-emergent FN | 5 Participants |
| Part A | Febrile Neutropenia (FN) Rate (Part A) | Grade 3 or higher treatment-related treatment-emergent FN | 5 Participants |
Secondary
Actual Dose Intensity: Brentuximab Vedotin (Part A)
Time frame: 6.5 months
Population: For Part A, the full analysis set includes all participants who received at least 1 dose of A+AVD (any of the study drugs in the regimen).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A | Actual Dose Intensity: Brentuximab Vedotin (Part A) | 0.5 mg/kg/week | Standard Deviation 0.1 |
Secondary
Actual Dose Intensity: Doxorubicin, Vinblastine, Dacarbazine (Part A)
Time frame: 6.5 months
Population: For Part A, the full analysis set includes all participants who received at least 1 dose of A+AVD (any of the study drugs in the regimen).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Actual Dose Intensity: Doxorubicin, Vinblastine, Dacarbazine (Part A) | Doxorubicin | 11.8 mg/m2/week | Standard Deviation 1 |
| Part A | Actual Dose Intensity: Doxorubicin, Vinblastine, Dacarbazine (Part A) | Vinblastine | 2.7 mg/m2/week | Standard Deviation 0.4 |
| Part A | Actual Dose Intensity: Doxorubicin, Vinblastine, Dacarbazine (Part A) | Dacarbazine | 176.3 mg/m2/week | Standard Deviation 15.2 |
Secondary
Complete Response Rate (Part A)
The complete response rate is defined as the percentage of participants with CR at EOT according to the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas (Cheson 2014).
Time frame: 7.2 months
Population: For Part A, the full analysis set includes all participants who received at least 1 dose of A+AVD (any of the study drugs in the regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A | Complete Response Rate (Part A) | 80 percentage of participants |
Secondary
Duration of Complete Response (DOCR) (Parts B and C)
DOCR was defined as the time from start of the first documentation of CR to the first documentation of tumor progression (per the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016) or death, whichever came first. DOCR was calculated for the subgroup of participants achieving CR. Participants without progression or death were censored on the date of the last radiological assessment of measured lesions. Kaplan-Meier method was used.
Time frame: Up to 51.1 months
Population: For Parts B and C, the full analysis set includes all participants who were enrolled and received any amount of the combination therapy in the study. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A | Duration of Complete Response (DOCR) (Parts B and C) | NA Months |
| Part C | Duration of Complete Response (DOCR) (Parts B and C) | NA Months |
Secondary
Duration of Response (DOR) at End of Study (Parts B and C)
DOR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression per the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016) or death, whichever came first. Duration of response was only calculated for the subgroup of participants achieving a CR or PR. Participants without progression or death were censored on the date of the last radiological assessment of measured lesions. Kaplan-Meier method was used.
Time frame: Up to 51.1 months
Population: For Parts B and C, the full analysis set includes all participants who were enrolled and received any amount of the combination therapy in the study. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A | Duration of Response (DOR) at End of Study (Parts B and C) | NA Months |
| Part C | Duration of Response (DOR) at End of Study (Parts B and C) | NA Months |
Secondary
Event Free Survival (EFS) Rate (Parts B and C)
EFS was defined as the time from the start of study treatment to the first documentation of objective tumor progression, death due to any cause, or receipt of subsequent anticancer therapy to treat residual or progressive disease, whichever occurred first. The determination of antitumor activity will be based on objective response assessments made according to Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016). Participants without progression or death were censored on the date of the last radiological assessment of measured lesions. EFS rate was percentage of participants with EFS.
Time frame: Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42
Population: For Parts B and C, the full analysis set includes all participants who were enrolled and received any amount of the combination therapy in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A | Event Free Survival (EFS) Rate (Parts B and C) | Month 3 | 98.25 Percentage of participants |
| Part A | Event Free Survival (EFS) Rate (Parts B and C) | Month 6 | 98.25 Percentage of participants |
| Part A | Event Free Survival (EFS) Rate (Parts B and C) | Month 9 | 94.67 Percentage of participants |
| Part A | Event Free Survival (EFS) Rate (Parts B and C) | Month 12 | 92.89 Percentage of participants |
| Part A | Event Free Survival (EFS) Rate (Parts B and C) | Month 15 | 91.03 Percentage of participants |
| Part A | Event Free Survival (EFS) Rate (Parts B and C) | Month 18 | 91.03 Percentage of participants |
| Part A | Event Free Survival (EFS) Rate (Parts B and C) | Month 21 | 86.89 Percentage of participants |
| Part A | Event Free Survival (EFS) Rate (Parts B and C) | Month 24 | 86.89 Percentage of participants |
| Part A | Event Free Survival (EFS) Rate (Parts B and C) | Month 27 | 86.89 Percentage of participants |
| Part A | Event Free Survival (EFS) Rate (Parts B and C) | Month 30 | 86.89 Percentage of participants |
| Part A | Event Free Survival (EFS) Rate (Parts B and C) | Month 33 | 84.54 Percentage of participants |
| Part A | Event Free Survival (EFS) Rate (Parts B and C) | Month 36 | 84.54 Percentage of participants |
| Part A | Event Free Survival (EFS) Rate (Parts B and C) | Month 39 | 84.54 Percentage of participants |
| Part A | Event Free Survival (EFS) Rate (Parts B and C) | Month 42 | 84.54 Percentage of participants |
| Part C | Event Free Survival (EFS) Rate (Parts B and C) | Month 3 | 100 Percentage of participants |
| Part C | Event Free Survival (EFS) Rate (Parts B and C) | Month 36 | 94.72 Percentage of participants |
| Part C | Event Free Survival (EFS) Rate (Parts B and C) | Month 6 | 98.66 Percentage of participants |
| Part C | Event Free Survival (EFS) Rate (Parts B and C) | Month 24 | 95.62 Percentage of participants |
| Part C | Event Free Survival (EFS) Rate (Parts B and C) | Month 9 | 98.66 Percentage of participants |
| Part C | Event Free Survival (EFS) Rate (Parts B and C) | Month 33 | 94.72 Percentage of participants |
| Part C | Event Free Survival (EFS) Rate (Parts B and C) | Month 12 | 98.66 Percentage of participants |
| Part C | Event Free Survival (EFS) Rate (Parts B and C) | Month 27 | 94.72 Percentage of participants |
| Part C | Event Free Survival (EFS) Rate (Parts B and C) | Month 15 | 97.95 Percentage of participants |
| Part C | Event Free Survival (EFS) Rate (Parts B and C) | Month 39 | 94.72 Percentage of participants |
| Part C | Event Free Survival (EFS) Rate (Parts B and C) | Month 18 | 96.46 Percentage of participants |
| Part C | Event Free Survival (EFS) Rate (Parts B and C) | Month 30 | 94.72 Percentage of participants |
| Part C | Event Free Survival (EFS) Rate (Parts B and C) | Month 21 | 96.46 Percentage of participants |
Secondary
Incidence of Adverse Events (Parts B and C)
Time frame: 8.9 months
Population: For Parts B and C, the full analysis set includes all participants who enrolled and received any amount of the combination therapy in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Incidence of Adverse Events (Parts B and C) | Any treatment-emergent adverse event (TEAE) | 57 Participants |
| Part A | Incidence of Adverse Events (Parts B and C) | Treatment-related treatment-emergent SAE | 8 Participants |
| Part A | Incidence of Adverse Events (Parts B and C) | Grade 3 or higher treatment-related TEAE | 19 Participants |
| Part A | Incidence of Adverse Events (Parts B and C) | Participants who discontinued treatment due to TEAE | 4 Participants |
| Part A | Incidence of Adverse Events (Parts B and C) | Grade 3 or higher TEAE | 29 Participants |
| Part A | Incidence of Adverse Events (Parts B and C) | Participants who discontinued treatment due to treatment-related TEAE | 4 Participants |
| Part A | Incidence of Adverse Events (Parts B and C) | Any treatment-emergent serious adverse event (SAE) | 15 Participants |
| Part A | Incidence of Adverse Events (Parts B and C) | TEAE leading to death | 0 Participants |
| Part A | Incidence of Adverse Events (Parts B and C) | Treatment-related TEAE | 56 Participants |
| Part C | Incidence of Adverse Events (Parts B and C) | TEAE leading to death | 0 Participants |
| Part C | Incidence of Adverse Events (Parts B and C) | Any treatment-emergent adverse event (TEAE) | 153 Participants |
| Part C | Incidence of Adverse Events (Parts B and C) | Treatment-related TEAE | 149 Participants |
| Part C | Incidence of Adverse Events (Parts B and C) | Grade 3 or higher TEAE | 67 Participants |
| Part C | Incidence of Adverse Events (Parts B and C) | Grade 3 or higher treatment-related TEAE | 52 Participants |
| Part C | Incidence of Adverse Events (Parts B and C) | Any treatment-emergent serious adverse event (SAE) | 29 Participants |
| Part C | Incidence of Adverse Events (Parts B and C) | Treatment-related treatment-emergent SAE | 19 Participants |
| Part C | Incidence of Adverse Events (Parts B and C) | Participants who discontinued treatment due to TEAE | 4 Participants |
| Part C | Incidence of Adverse Events (Parts B and C) | Participants who discontinued treatment due to treatment-related TEAE | 4 Participants |
Secondary
Incidence of Laboratory Abnormalities (Parts B and C)
Laboratory values were graded according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.03). As per NCI CTCAE version 4.03 grading, Grade 1 indicated mild or asymptomatic laboratory abnormalities, Grade 2 indicated moderate laboratory abnormalities, and Grade 3 indicated severe and 4 indicated life-threatening laboratory abnormalities.
Time frame: 8.9 months
Population: For Parts B and C, the full analysis set included all participants who enrolled and received any amount of the combination therapy in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin high, Grade 2 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin low, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Neutrophils low, Grade 3 | 4 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin low, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes low, Grade 1 | 19 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium high, Grade 1 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Neutrophils low, Grade 4 | 2 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium high, Grade 2 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin low, Grade 2 | 10 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium high, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Platelets low, Grade 1 | 6 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Platelets low, Grade 2 | 1 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium low, Grade 1 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes low, Grade 2 | 12 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium low, Grade 2 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Platelets low, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium low, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Alkaline phosphatase high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium low, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Platelets low, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Creatinine high, Grade 1 | 47 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes low, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Alanine aminotransferase high, Grade 1 | 26 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Creatinine high, Grade 2 | 5 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin low, Grade 3 | 1 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Creatinine high, Grade 3 | 1 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Alanine aminotransferase high, Grade 2 | 3 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Creatinine high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes low, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Estimated glomerular filtration rate low, Grade 1 | 1 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Alanine aminotransferase high, Grade 3 | 4 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Estimated glomerular filtration rate low, Grade 2 | 4 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin high, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Estimated glomerular filtration rate low, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Estimated glomerular filtration rate low, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Alanine aminotransferase high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose high, Grade 1 | 45 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes high, Grade 1 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose high, Grade 2 | 5 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Albumin low, Grade 1 | 11 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose high, Grade 3 | 1 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin low, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Albumin low, Grade 2 | 3 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose low, Grade 1 | 12 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Albumin low, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose low, Grade 2 | 1 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes high, Grade 2 | 1 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose low, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Alkaline phosphatase high, Grade 1 | 30 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose low, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin high, Grade 1 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Lipase high, Grade 1 | 9 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Alkaline phosphatase high, Grade 2 | 2 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Lipase high, Grade 2 | 1 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes high, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Lipase high, Grade 3 | 5 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Alkaline phosphatase high, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Lipase high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes high, Grade 1 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Phosphate low, Grade 1 | 1 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Amylase high, Grade 1 | 3 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Phosphate low, Grade 2 | 7 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Phosphate low, Grade 3 | 2 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Amylase high, Grade 2 | 2 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Phosphate low, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium high, Grade 1 | 3 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Amylase high, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium high, Grade 2 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes low, Grade 1 | 11 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium high, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Amylase high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes high, Grade 2 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium low, Grade 1 | 9 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes low, Grade 2 | 17 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium low, Grade 2 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Aspartate aminotransferase high, Grade 1 | 27 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium low, Grade 3 | 2 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Albumin low, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium low, Grade 4 | 1 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Aspartate aminotransferase high, Grade 2 | 1 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium high, Grade 1 | 2 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes low, Grade 3 | 7 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium high, Grade 2 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Aspartate aminotransferase high, Grade 3 | 2 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium high, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose high, Grade 4 | 1 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes high, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium low, Grade 1 | 11 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Aspartate aminotransferase high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium low, Grade 2 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes low, Grade 4 | 1 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium low, Grade 3 | 2 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin high, Grade 1 | 12 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium low, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin low, Grade 1 | 37 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Total bilirubin high, Grade 1 | 1 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin high, Grade 2 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Total bilirubin high, Grade 2 | 2 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Neutrophils low, Grade 1 | 4 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Total bilirubin high, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin high, Grade 3 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Total bilirubin high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Urate high, Grade 1 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Urate high, Grade 2 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin low, Grade 1 | 7 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Urate high, Grade 3 | 10 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Neutrophils low, Grade 2 | 14 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Urate high, Grade 4 | 0 Participants |
| Part A | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin low, Grade 2 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Urate high, Grade 4 | 1 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Albumin low, Grade 2 | 6 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Albumin low, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Alkaline phosphatase high, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin high, Grade 1 | 4 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin high, Grade 2 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin high, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin high, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin low, Grade 1 | 96 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin low, Grade 2 | 6 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin low, Grade 3 | 1 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Hemoglobin low, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes high, Grade 1 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes high, Grade 2 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes high, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes high, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes low, Grade 1 | 41 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes low, Grade 2 | 24 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes low, Grade 3 | 2 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Leukocytes low, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes high, Grade 1 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes high, Grade 2 | 3 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes high, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes high, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes low, Grade 1 | 31 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes low, Grade 2 | 22 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes low, Grade 3 | 9 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Lymphocytes low, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Neutrophils low, Grade 1 | 12 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Neutrophils low, Grade 2 | 38 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Neutrophils low, Grade 3 | 11 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Neutrophils low, Grade 4 | 3 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Platelets low, Grade 2 | 1 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Platelets low, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Platelets low, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Alanine aminotransferase high, Grade 1 | 71 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Alanine aminotransferase high, Grade 2 | 16 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Alanine aminotransferase high, Grade 3 | 10 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Alanine aminotransferase high, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Albumin low, Grade 1 | 22 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Albumin low, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Alkaline phosphatase high, Grade 1 | 51 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Alkaline phosphatase high, Grade 2 | 1 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Alkaline phosphatase high, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Amylase high, Grade 1 | 15 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Amylase high, Grade 2 | 6 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Amylase high, Grade 3 | 6 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Amylase high, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin high, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Aspartate aminotransferase high, Grade 1 | 75 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Aspartate aminotransferase high, Grade 2 | 7 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Aspartate aminotransferase high, Grade 3 | 1 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Aspartate aminotransferase high, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin high, Grade 1 | 18 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin high, Grade 2 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin high, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin low, Grade 1 | 5 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin low, Grade 2 | 1 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin low, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Calcium corrected for albumin low, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium high, Grade 1 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium high, Grade 2 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium high, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium high, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium low, Grade 1 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium low, Grade 2 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium low, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Ionized calcium low, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Estimated glomerular filtration rate low, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Creatinine high, Grade 1 | 127 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Creatinine high, Grade 2 | 11 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Creatinine high, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Creatinine high, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Estimated glomerular filtration rate low, Grade 1 | 8 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Estimated glomerular filtration rate low, Grade 2 | 10 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Estimated glomerular filtration rate low, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose high, Grade 1 | 69 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose high, Grade 2 | 9 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose high, Grade 3 | 13 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose high, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose low, Grade 1 | 18 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose low, Grade 2 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose low, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Glucose low, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Lipase high, Grade 1 | 13 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Lipase high, Grade 2 | 6 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Lipase high, Grade 3 | 6 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Lipase high, Grade 4 | 3 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Phosphate low, Grade 1 | 3 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Phosphate low, Grade 2 | 9 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Phosphate low, Grade 3 | 4 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Phosphate low, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium high, Grade 1 | 7 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium high, Grade 2 | 1 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium high, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium high, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium low, Grade 1 | 19 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium low, Grade 2 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium low, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Potassium low, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium high, Grade 1 | 3 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium high, Grade 2 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium high, Grade 3 | 1 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium high, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium low, Grade 1 | 25 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium low, Grade 2 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium low, Grade 3 | 2 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Sodium low, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Total bilirubin high, Grade 1 | 8 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Total bilirubin high, Grade 2 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Total bilirubin high, Grade 3 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Total bilirubin high, Grade 4 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Urate high, Grade 1 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Urate high, Grade 2 | 0 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Urate high, Grade 3 | 28 Participants |
| Part C | Incidence of Laboratory Abnormalities (Parts B and C) | Platelets low, Grade 1 | 22 Participants |
Secondary
Number of Participants With Adverse Events of Clinical Interest (AECI) (Part A)
An adverse event (AE) was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with the treatment. Participants with peripheral neuropathy (PN) adverse events were summarized under AECI.
Time frame: Approximately up to 7.5 months
Population: For Part A, the full analysis set included all participants who received at least 1 dose of A+AVD (any of the study drugs in the regimen).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A | Number of Participants With Adverse Events of Clinical Interest (AECI) (Part A) | 32 Participants |
Secondary
Number of Participants With Subsequent Anticancer Therapy Utilization (Part A)
Number of participants with subsequent anticancer therapy have been reported in this outcome measure.
Time frame: 33.8 months
Population: For Part A, the full analysis set includes all participants who received at least 1 dose of A+AVD (any of the study drugs in the regimen).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Number of Participants With Subsequent Anticancer Therapy Utilization (Part A) | Participants with any subsequent therapy | 6 Participants |
| Part A | Number of Participants With Subsequent Anticancer Therapy Utilization (Part A) | Consolidative radiotherapy: Radiotherapy | 3 Participants |
| Part A | Number of Participants With Subsequent Anticancer Therapy Utilization (Part A) | Consolidative radiotherapy: Proton radiation | 1 Participants |
| Part A | Number of Participants With Subsequent Anticancer Therapy Utilization (Part A) | Immunotherapy: Nivolumab | 1 Participants |
| Part A | Number of Participants With Subsequent Anticancer Therapy Utilization (Part A) | Maintenance: Nivolumab | 1 Participants |
| Part A | Number of Participants With Subsequent Anticancer Therapy Utilization (Part A) | Maintenance radiotherapy: Radiation therapy | 1 Participants |
| Part A | Number of Participants With Subsequent Anticancer Therapy Utilization (Part A) | Systemic therapy for progressive disease: Bendamustine monotherapy | 1 Participants |
| Part A | Number of Participants With Subsequent Anticancer Therapy Utilization (Part A) | Systemic therapy for relapsed disease: Nivolumab | 1 Participants |
Secondary
Overall Response Rate (ORR) at EOT (Parts B and C)
ORR is defined as the percentage of participants with CR or partial response (PR) at EOT according to the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016) in participants with previously untreated cHL.
Time frame: Up to 7.8 months
Population: For Parts B and C, the full analysis set included all participants who were enrolled and received any amount of the combination therapy in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A | Overall Response Rate (ORR) at EOT (Parts B and C) | 93 Percentage of participants |
| Part C | Overall Response Rate (ORR) at EOT (Parts B and C) | 96 Percentage of participants |
Secondary
Overall Survival (OS) Rate (Parts B and C)
OS was defined as the time from start of study treatment to date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. Kaplan-Meier method was used.
Time frame: At months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42 from the start of study treatment
Population: For Parts B and C, the full analysis set includes all participants who were enrolled and received any amount of the combination therapy in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A | Overall Survival (OS) Rate (Parts B and C) | Month 12 | 98.25 Percentage of participants |
| Part A | Overall Survival (OS) Rate (Parts B and C) | Month 24 | 98.25 Percentage of participants |
| Part A | Overall Survival (OS) Rate (Parts B and C) | Month 3 | 100 Percentage of participants |
| Part A | Overall Survival (OS) Rate (Parts B and C) | Month 27 | 98.25 Percentage of participants |
| Part A | Overall Survival (OS) Rate (Parts B and C) | Month 15 | 98.25 Percentage of participants |
| Part A | Overall Survival (OS) Rate (Parts B and C) | Month 30 | 98.25 Percentage of participants |
| Part A | Overall Survival (OS) Rate (Parts B and C) | Month 9 | 100 Percentage of participants |
| Part A | Overall Survival (OS) Rate (Parts B and C) | Month 33 | 98.25 Percentage of participants |
| Part A | Overall Survival (OS) Rate (Parts B and C) | Month 18 | 98.25 Percentage of participants |
| Part A | Overall Survival (OS) Rate (Parts B and C) | Month 36 | 98.25 Percentage of participants |
| Part A | Overall Survival (OS) Rate (Parts B and C) | Month 6 | 100 Percentage of participants |
| Part A | Overall Survival (OS) Rate (Parts B and C) | Month 39 | 98.25 Percentage of participants |
| Part A | Overall Survival (OS) Rate (Parts B and C) | Month 21 | 98.25 Percentage of participants |
| Part A | Overall Survival (OS) Rate (Parts B and C) | Month 42 | 98.25 Percentage of participants |
| Part C | Overall Survival (OS) Rate (Parts B and C) | Month 42 | 98.73 Percentage of participants |
| Part C | Overall Survival (OS) Rate (Parts B and C) | Month 3 | 100 Percentage of participants |
| Part C | Overall Survival (OS) Rate (Parts B and C) | Month 6 | 100 Percentage of participants |
| Part C | Overall Survival (OS) Rate (Parts B and C) | Month 9 | 100 Percentage of participants |
| Part C | Overall Survival (OS) Rate (Parts B and C) | Month 12 | 100 Percentage of participants |
| Part C | Overall Survival (OS) Rate (Parts B and C) | Month 15 | 100 Percentage of participants |
| Part C | Overall Survival (OS) Rate (Parts B and C) | Month 18 | 100 Percentage of participants |
| Part C | Overall Survival (OS) Rate (Parts B and C) | Month 21 | 100 Percentage of participants |
| Part C | Overall Survival (OS) Rate (Parts B and C) | Month 24 | 100 Percentage of participants |
| Part C | Overall Survival (OS) Rate (Parts B and C) | Month 27 | 100 Percentage of participants |
| Part C | Overall Survival (OS) Rate (Parts B and C) | Month 30 | 100 Percentage of participants |
| Part C | Overall Survival (OS) Rate (Parts B and C) | Month 33 | 98.73 Percentage of participants |
| Part C | Overall Survival (OS) Rate (Parts B and C) | Month 36 | 98.73 Percentage of participants |
| Part C | Overall Survival (OS) Rate (Parts B and C) | Month 39 | 98.73 Percentage of participants |
Secondary
PFS Rate (Parts B and C)
PFS was defined as the time from start of study treatment to first documentation of objective tumor progression or death. The determination of antitumor activity will be based on objective response assessments made according to Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016). Participants without progression or death were censored on the date of the last radiological assessment of measured lesions. Kaplan-Meier method was used.
Time frame: At months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42 from the start of study treatment
Population: For Parts B and C, the full analysis set includes all participants who were enrolled and received any amount of the combination therapy in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A | PFS Rate (Parts B and C) | Month 3 | 100 Percentage of participants |
| Part A | PFS Rate (Parts B and C) | Month 6 | 100 Percentage of participants |
| Part A | PFS Rate (Parts B and C) | Month 9 | 96.36 Percentage of participants |
| Part A | PFS Rate (Parts B and C) | Month 12 | 94.55 Percentage of participants |
| Part A | PFS Rate (Parts B and C) | Month 15 | 92.65 Percentage of participants |
| Part A | PFS Rate (Parts B and C) | Month 18 | 92.65 Percentage of participants |
| Part A | PFS Rate (Parts B and C) | Month 21 | 88.44 Percentage of participants |
| Part A | PFS Rate (Parts B and C) | Month 24 | 88.44 Percentage of participants |
| Part A | PFS Rate (Parts B and C) | Month 27 | 88.44 Percentage of participants |
| Part A | PFS Rate (Parts B and C) | Month 30 | 88.44 Percentage of participants |
| Part A | PFS Rate (Parts B and C) | Month 33 | 86.05 Percentage of participants |
| Part A | PFS Rate (Parts B and C) | Month 36 | 86.05 Percentage of participants |
| Part A | PFS Rate (Parts B and C) | Month 39 | 86.05 Percentage of participants |
| Part A | PFS Rate (Parts B and C) | Month 42 | 86.05 Percentage of participants |
| Part C | PFS Rate (Parts B and C) | Month 3 | 100 Percentage of participants |
| Part C | PFS Rate (Parts B and C) | Month 36 | 96.01 Percentage of participants |
| Part C | PFS Rate (Parts B and C) | Month 6 | 100 Percentage of participants |
| Part C | PFS Rate (Parts B and C) | Month 24 | 96.92 Percentage of participants |
| Part C | PFS Rate (Parts B and C) | Month 9 | 100 Percentage of participants |
| Part C | PFS Rate (Parts B and C) | Month 33 | 96.01 Percentage of participants |
| Part C | PFS Rate (Parts B and C) | Month 12 | 100 Percentage of participants |
| Part C | PFS Rate (Parts B and C) | Month 27 | 96.01 Percentage of participants |
| Part C | PFS Rate (Parts B and C) | Month 15 | 99.29 Percentage of participants |
| Part C | PFS Rate (Parts B and C) | Month 39 | 96.01 Percentage of participants |
| Part C | PFS Rate (Parts B and C) | Month 18 | 97.77 Percentage of participants |
| Part C | PFS Rate (Parts B and C) | Month 30 | 96.01 Percentage of participants |
| Part C | PFS Rate (Parts B and C) | Month 21 | 97.77 Percentage of participants |
Secondary
Physician-reported Progression Free Survival (PFS) (Part A)
The physician-reported PFS rate at 2 years is estimated based on Kaplan-Meier methodology. The determination of antitumor activity will be based on response assessments made according to the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas (Cheson 2014).
Time frame: 24 months
Population: For Part A, the full analysis set includes all participants who received at least 1 dose of A+AVD (any of the study drugs in the regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A | Physician-reported Progression Free Survival (PFS) (Part A) | 89.23 percentage of participants |
Secondary
Primary Refractory Disease Rate (Part A)
The primary refractory disease rate is defined as the percentage of participants with less than complete response or relapse within 3 months of EOT, according to the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas
Time frame: 10.2 months
Population: For Part A, the full analysis set includes all participants who received at least 1 dose of A+AVD (any of the study drugs in the regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A | Primary Refractory Disease Rate (Part A) | 10 percentage of participants |
Secondary
Rate of Dose Reduction and Delays: Brentuximab Vedotin (Part A)
Time frame: 6.5 months
Population: For Part A, the full analysis set includes all participants who received at least 1 dose of A+AVD (any of the study drugs in the regimen).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Rate of Dose Reduction and Delays: Brentuximab Vedotin (Part A) | Participants with any dose modification | 29 Participants |
| Part A | Rate of Dose Reduction and Delays: Brentuximab Vedotin (Part A) | Participants with any dose delay | 22 Participants |
| Part A | Rate of Dose Reduction and Delays: Brentuximab Vedotin (Part A) | Participants with any dose delay due to AE | 15 Participants |
| Part A | Rate of Dose Reduction and Delays: Brentuximab Vedotin (Part A) | Participants with any dose delay due to other reason | 14 Participants |
| Part A | Rate of Dose Reduction and Delays: Brentuximab Vedotin (Part A) | Participants with any dose reduction due to AE | 14 Participants |
Secondary
Rate of Dose Reduction and Delays: Dacarbazine (Part A)
Time frame: 6.5 months
Population: For Part A, the full analysis set includes all participants who received at least 1 dose of A+AVD (any of the study drugs in the regimen).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Rate of Dose Reduction and Delays: Dacarbazine (Part A) | Participants with any dose modification | 25 Participants |
| Part A | Rate of Dose Reduction and Delays: Dacarbazine (Part A) | Participants with any dose delay | 22 Participants |
| Part A | Rate of Dose Reduction and Delays: Dacarbazine (Part A) | Participants with any dose delay due to AE | 15 Participants |
| Part A | Rate of Dose Reduction and Delays: Dacarbazine (Part A) | Participants with any dose delay due to other reason | 14 Participants |
| Part A | Rate of Dose Reduction and Delays: Dacarbazine (Part A) | Participants with any dose reduction due to AE | 6 Participants |
Secondary
Rate of Dose Reduction and Delays: Doxorubicin (Part A)
Time frame: 6.5 months
Population: For Part A, the full analysis set includes all participants who received at least 1 dose of A+AVD (any of the study drugs in the regimen).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Rate of Dose Reduction and Delays: Doxorubicin (Part A) | Participants with any dose modification | 25 Participants |
| Part A | Rate of Dose Reduction and Delays: Doxorubicin (Part A) | Participants with any dose delay | 23 Participants |
| Part A | Rate of Dose Reduction and Delays: Doxorubicin (Part A) | Participants with any dose delay due to AE | 15 Participants |
| Part A | Rate of Dose Reduction and Delays: Doxorubicin (Part A) | Participants with any dose delay due to other reason | 15 Participants |
| Part A | Rate of Dose Reduction and Delays: Doxorubicin (Part A) | Participants with any dose reduction due to AE | 7 Participants |
Secondary
Rate of Dose Reduction and Delays: Vinblastine (Part A)
Time frame: 6.5 months
Population: For Part A, the full analysis set includes all participants who received at least 1 dose of A+AVD (any of the study drugs in the regimen).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Rate of Dose Reduction and Delays: Vinblastine (Part A) | Participants with any dose modification | 27 Participants |
| Part A | Rate of Dose Reduction and Delays: Vinblastine (Part A) | Participants with any dose delay | 22 Participants |
| Part A | Rate of Dose Reduction and Delays: Vinblastine (Part A) | Participants with any dose delay due to AE | 15 Participants |
| Part A | Rate of Dose Reduction and Delays: Vinblastine (Part A) | Participants with any dose delay due to other reason | 14 Participants |
| Part A | Rate of Dose Reduction and Delays: Vinblastine (Part A) | Participants with any dose reduction due to AE | 12 Participants |
Secondary
Relative Dose Intensity (Part A)
Time frame: 6.5 months
Population: For Part A, the full analysis set includes all participants who received at least 1 dose of A+AVD (any of the study drugs in the regimen).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Relative Dose Intensity (Part A) | Vinblastine | 89.0 percentage of intended dose | Standard Deviation 13.6 |
| Part A | Relative Dose Intensity (Part A) | Brentuximab vedotin | 91.0 percentage of intended dose | Standard Deviation 10.8 |
| Part A | Relative Dose Intensity (Part A) | Doxorubicin | 94.2 percentage of intended dose | Standard Deviation 8.2 |
| Part A | Relative Dose Intensity (Part A) | Dacarbazine | 94.0 percentage of intended dose | Standard Deviation 8.1 |