Hodgkin Lymphoma
Conditions
Keywords
Monomethyl auristatin E, Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Immunotherapy, Autologous stem cell transplant
Brief summary
The purpose of this study is to assess the safety profile and antitumor activity of brentuximab vedotin administered in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma (HL)
Detailed description
This study will examine the safety profile and antitumor activity when brentuximab vedotin is combined with nivolumab. Patients will be treated for up to four 21-day cycles with brentuximab vedotin 1.8 mg/kg and nivolumab 3 mg/kg. There will be 3 parts to this study. In Part 1, the safety of combination treatment will be evaluated by a Safety Monitoring Committee (SMC) prior to expansion of enrollment to evaluate treatment effect in Part 2. Part 2 of the study will further characterize the safety and antitumor activity of brentuximab vedotin combined with nivolumab by enrolling patients at the recommended dose schedule determined in Part 1. Part 3 of the study will evaluate the safety and antitumor activity of combination treatment administered at an alternate dosing schedule determined by cumulative safety and activity data from Parts 1 and 2.
Interventions
DRUGbrentuximab vedotin
1.8 mg/kg by intravenous (IV) infusion for up to 4 cycles
DRUGnivolumab
3 mg/kg by intravenous (IV) infusion for up to 4 cycles
Sponsors
Bristol-Myers Squibb
Seagen Inc.
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
* Relapsed or refractory Hodgkin lymphoma following failure of standard frontline chemotherapy for the treatment of classical Hodgkin lymphoma * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion criteria
* Previously treated with brentuximab vedotin, immune-oncology agents, or received an allogeneic or autologous stem cell transplant * Documented history of a cerebral vascular event * History of another invasive malignancy that has not been in remission for at least 3 years * History of progressive multifocal leukoencephalopathy (PML)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Up to 28.9 months | Treatment-emergent adverse events (TEAEs) are presented and defined as newly occurring (not present at baseline) or worsening after first dose of investigational product. The timeframe includes a 6.01 month safety reporting period and additional long-term follow up through 28.9 months. |
| Complete Remission Rate | Up to 3.42 months | Number of patients with complete metabolic response (CMR) at end of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Up to 3.42 months | Number of patients with complete metabolic response (CMR) or partial metabolic response (PMR) |
| Duration of Complete Response | Up to 69.3 months | The time from start of the first documentation of complete response (CR) to the first documentation of tumor progression (PD) including radiographic evidence of progression and clinical progression per investigator or to death due to any cause, whichever comes first. |
| Duration of Objective Response | Up to 69.3 months | The time from start of the first documentation of OR (CR or PR) to the first documentation of PD or to death due to any cause, whichever comes first. |
| Progression-free Survival Post-autologous Stem Cell Transplant | Up to 67.3 months | For participants who undergo ASCT, the time from ASCT to the first documentation of PD or to death due to any cause, whichever comes first. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Staggered Dose Brentuximab vedotin plus nivolumab; staggered dose in Cycle 1 only. brentuximab vedotin: 1.8 mg/kg by intravenous (IV) infusion for up to 4 cycles nivolumab: 3 mg/kg by intravenous (IV) infusion for up to 4 cycles | 6 |
| Part 2: Staggered Dose Expansion Brentuximab vedotin plus nivolumab; staggered dose in Cycle 1 only. brentuximab vedotin: 1.8 mg/kg by intravenous (IV) infusion for up to 4 cycles nivolumab: 3 mg/kg by intravenous (IV) infusion for up to 4 cycles | 55 |
| Part 3: Same-day Dose Brentuximab vedotin plus nivolumab brentuximab vedotin: 1.8 mg/kg by intravenous (IV) infusion for up to 4 cycles nivolumab: 3 mg/kg by intravenous (IV) infusion for up to 4 cycles | 30 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 8 | 3 |
| Overall Study | Did not meet inclusion criteria | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 5 | 3 |
| Overall Study | Study closure by Sponsor | 4 | 40 | 24 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | Total | Part 3: Same-day Dose | Part 2: Staggered Dose Expansion | Part 1: Staggered Dose |
|---|---|---|---|---|
| Age, Continuous | 34.0 years | 31.5 years | 37.0 years | 26.0 years |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0 | 58 Participants | 19 Participants | 35 Participants | 4 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1 | 32 Participants | 10 Participants | 20 Participants | 2 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Unknown | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 9 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 74 Participants | 20 Participants | 49 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 2 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 2 Participants | 2 Participants | 0 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 | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 77 Participants | 24 Participants | 47 Participants | 6 Participants |
| Sex: Female, Male Female | 51 Participants | 19 Participants | 27 Participants | 5 Participants |
| Sex: Female, Male Male | 40 Participants | 11 Participants | 28 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 8 / 56 | 3 / 31 |
| other Total, other adverse events | 6 / 6 | 55 / 55 | 30 / 30 |
| serious Total, serious adverse events | 0 / 6 | 16 / 55 | 5 / 30 |
Outcome results
Primary
Complete Remission Rate
Number of patients with complete metabolic response (CMR) at end of treatment
Time frame: Up to 3.42 months
Population: The Efficacy Evaluable analysis set includes all patients who had an adequate baseline disease assessment, received any amount of either drug, and subsequently had an adequate response assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Staggered Dose | Complete Remission Rate | 4 Participants |
| Part 2: Staggered Dose Expansion | Complete Remission Rate | 33 Participants |
| Part 3: Same-day Dose | Complete Remission Rate | 24 Participants |
Primary
Number of Participants With Adverse Events (AEs)
Treatment-emergent adverse events (TEAEs) are presented and defined as newly occurring (not present at baseline) or worsening after first dose of investigational product. The timeframe includes a 6.01 month safety reporting period and additional long-term follow up through 28.9 months.
Time frame: Up to 28.9 months
Population: The safety analysis set includes all patients who receive any amount of brentuximab vedotin or nivolumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Staggered Dose | Number of Participants With Adverse Events (AEs) | SAE related to nivolumab only | 0 Participants |
| Part 1: Staggered Dose | Number of Participants With Adverse Events (AEs) | AEs related to brentuximab vedotin only | 5 Participants |
| Part 1: Staggered Dose | Number of Participants With Adverse Events (AEs) | SAEs related to brentuximab vedotin only | 0 Participants |
| Part 1: Staggered Dose | Number of Participants With Adverse Events (AEs) | AEs related to both study drugs | 5 Participants |
| Part 1: Staggered Dose | Number of Participants With Adverse Events (AEs) | AEs related to nivolumab only | 3 Participants |
| Part 1: Staggered Dose | Number of Participants With Adverse Events (AEs) | AEs leading to treatment discontinuation | 0 Participants |
| Part 1: Staggered Dose | Number of Participants With Adverse Events (AEs) | SAE related to both study drugs | 0 Participants |
| Part 1: Staggered Dose | Number of Participants With Adverse Events (AEs) | Any serious adverse event (SAE) | 0 Participants |
| Part 1: Staggered Dose | Number of Participants With Adverse Events (AEs) | Any treatment-emergent adverse event (TEAE) | 6 Participants |
| Part 2: Staggered Dose Expansion | Number of Participants With Adverse Events (AEs) | SAE related to nivolumab only | 4 Participants |
| Part 2: Staggered Dose Expansion | Number of Participants With Adverse Events (AEs) | SAE related to both study drugs | 5 Participants |
| Part 2: Staggered Dose Expansion | Number of Participants With Adverse Events (AEs) | AEs leading to treatment discontinuation | 1 Participants |
| Part 2: Staggered Dose Expansion | Number of Participants With Adverse Events (AEs) | Any treatment-emergent adverse event (TEAE) | 55 Participants |
| Part 2: Staggered Dose Expansion | Number of Participants With Adverse Events (AEs) | AEs related to brentuximab vedotin only | 41 Participants |
| Part 2: Staggered Dose Expansion | Number of Participants With Adverse Events (AEs) | AEs related to nivolumab only | 20 Participants |
| Part 2: Staggered Dose Expansion | Number of Participants With Adverse Events (AEs) | AEs related to both study drugs | 37 Participants |
| Part 2: Staggered Dose Expansion | Number of Participants With Adverse Events (AEs) | Any serious adverse event (SAE) | 16 Participants |
| Part 2: Staggered Dose Expansion | Number of Participants With Adverse Events (AEs) | SAEs related to brentuximab vedotin only | 2 Participants |
| Part 3: Same-day Dose | Number of Participants With Adverse Events (AEs) | AEs related to both study drugs | 27 Participants |
| Part 3: Same-day Dose | Number of Participants With Adverse Events (AEs) | AEs leading to treatment discontinuation | 1 Participants |
| Part 3: Same-day Dose | Number of Participants With Adverse Events (AEs) | SAE related to nivolumab only | 0 Participants |
| Part 3: Same-day Dose | Number of Participants With Adverse Events (AEs) | Any serious adverse event (SAE) | 5 Participants |
| Part 3: Same-day Dose | Number of Participants With Adverse Events (AEs) | SAE related to both study drugs | 4 Participants |
| Part 3: Same-day Dose | Number of Participants With Adverse Events (AEs) | Any treatment-emergent adverse event (TEAE) | 30 Participants |
| Part 3: Same-day Dose | Number of Participants With Adverse Events (AEs) | AEs related to nivolumab only | 13 Participants |
| Part 3: Same-day Dose | Number of Participants With Adverse Events (AEs) | AEs related to brentuximab vedotin only | 15 Participants |
| Part 3: Same-day Dose | Number of Participants With Adverse Events (AEs) | SAEs related to brentuximab vedotin only | 0 Participants |
Secondary
Duration of Complete Response
The time from start of the first documentation of complete response (CR) to the first documentation of tumor progression (PD) including radiographic evidence of progression and clinical progression per investigator or to death due to any cause, whichever comes first.
Time frame: Up to 69.3 months
Population: The Efficacy Evaluable analysis set includes all patients who had an adequate baseline disease assessment, received any amount of either drug, and subsequently had an adequate response assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Staggered Dose | Duration of Complete Response | NA Months |
| Part 2: Staggered Dose Expansion | Duration of Complete Response | NA Months |
| Part 3: Same-day Dose | Duration of Complete Response | NA Months |
Secondary
Duration of Objective Response
The time from start of the first documentation of OR (CR or PR) to the first documentation of PD or to death due to any cause, whichever comes first.
Time frame: Up to 69.3 months
Population: The Efficacy Evaluable analysis set includes all patients who had an adequate baseline disease assessment, received any amount of either drug, and subsequently had an adequate response assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Staggered Dose | Duration of Objective Response | NA Months |
| Part 2: Staggered Dose Expansion | Duration of Objective Response | NA Months |
| Part 3: Same-day Dose | Duration of Objective Response | NA Months |
Secondary
Objective Response Rate
Number of patients with complete metabolic response (CMR) or partial metabolic response (PMR)
Time frame: Up to 3.42 months
Population: The Efficacy Evaluable analysis set includes all patients who had an adequate baseline disease assessment, received any amount of either drug, and subsequently had an adequate response assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Staggered Dose | Objective Response Rate | 6 Participants |
| Part 2: Staggered Dose Expansion | Objective Response Rate | 43 Participants |
| Part 3: Same-day Dose | Objective Response Rate | 28 Participants |
Secondary
Progression-free Survival Post-autologous Stem Cell Transplant
For participants who undergo ASCT, the time from ASCT to the first documentation of PD or to death due to any cause, whichever comes first.
Time frame: Up to 67.3 months
Population: Subset includes all patients who received any amount of brentuximab vedotin or nivolumab and who received a stem cell transplant without intervening salvage after study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Staggered Dose | Progression-free Survival Post-autologous Stem Cell Transplant | NA Months |
| Part 2: Staggered Dose Expansion | Progression-free Survival Post-autologous Stem Cell Transplant | NA Months |
| Part 3: Same-day Dose | Progression-free Survival Post-autologous Stem Cell Transplant | NA Months |