A Study of Brentuximab Vedotin Combined With Nivolumab for Relapsed or Refractory Hodgkin Lymphoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1/2 Study Evaluating Brentuximab Vedotin in Combination With Nivolumab in Patients With Relapsed or Refractory Hodgkin Lymphoma After Failure of Frontline Therapy

Conditions
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Hodgkin Lymphoma

Intervention / Treatment
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* Drug: brentuximab vedotin
* Drug: nivolumab


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brentuximab Vedotin + Nivolumab<br>Brentuximab vedotin plus nivolumab | Drug: brentuximab vedotin<br>* 1.8 mg/kg by intravenous (IV) infusion for up to 4 cycles<br>* Other names: SGN-35, ADCETRIS;Drug: nivolumab<br>* 3 mg/kg by intravenous (IV) infusion for up to 4 cycles<br>* Other names: BMS-936558, OPDIVO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 28.9 months | 
| Complete Remission Rate | Number of patients with complete metabolic response (CMR) at end of treatment | Up to 3.42 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Number of patients with complete metabolic response (CMR) or partial metabolic response (PMR) | Up to 3.42 months | 
| 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. | Up to 69.3 months | 
| 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. | Up to 69.3 months | 
| 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. | Up to 67.3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Monomethyl auristatin E, Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Immunotherapy, Autologous stem cell transplant