A Study of Coformulated Favezelimab/Pembrolizumab (MK-4280A) Versus Physician's Choice Chemotherapy in PD-(L)1-refractory, Relapsed or Refractory Classical Hodgkin Lymphoma (MK-4280A-008)

Study Overview
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Brief Summary
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The purpose of this study is to compare efficacy of coformulated favezelimab/pembrolizumab (MK-4280A) with physician's choice chemotherapy of bendamustine or gemcitabine in participants with PD-(L)1-refractory, relapsed or refractory classical Hodgkin Lymphoma. The study will also assess the safety and tolerability of coformulated favezelimab/pembrolizumab. The primary study hypotheses are that coformulated favezelimab/pembrolizumab is superior to physician's choice chemotherapy with respect to progression-free survival (PFS) and overall survival (OS).

Official Title
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A Phase 3 Randomized Clinical Study of MK-4280A (Coformulated Favezelimab [MK-4280] Plus Pembrolizumab [MK-3475]) Versus Physician's Choice Chemotherapy in PD-(L)1-refractory, Relapsed or Refractory Classical Hodgkin Lymphoma (KEYFORM-008)

Conditions
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Hodgkin Lymphoma

Intervention / Treatment
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* Biological: favezelimab/pembrolizumab
* Drug: bendamustine
* Drug: gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has histologically confirmed diagnosis of classical Hodgkin lymphoma (cHL) that is 2-fluorodeoxyglucose-avid (FDG-avid). Has relapsed (defined as disease progression after most recent therapy) or refractory (defined as failed to achieve CR or PR to most recent therapy) cHL and exhausted all available treatment options with known clinical benefit. Has progressed on treatment with an anti-PD-(L)1 monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. Submits an archival (<5 years) or newly obtained tumor tissue sample which has not been previously irradiated. Exclusion Criteria: Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy. History of central nervous system (CNS) metastases or active CNS involvement. Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Has an active infection requiring systemic treatment. History of hemophagocytic lymphohisticytosis. Has an active seizure disorder that is not well controlled. Has clinically significant (ie, active) cardiovascular disease. Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization. Received prior radiotherapy within 2 weeks of start of study intervention or radiation related toxicities requiring corticosteroids. Has not adequately recovered from major surgical procedure. Known additional malignancy that is progressing or has required active treatment within the past 3 years. History of human immunodeficiency virus (HIV). Has had an allogeneic hematopoietic stem cell or solid organ transplantation within the last 5 years.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Favezelimab/Pembrolizumab<br>Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) by intravenous (IV) infusion on Day 1, then every three weeks (Q3W), for up to 35 infusions. | Biological: favezelimab/pembrolizumab<br>* Coformulated favezelimab/pembrolizumab (800 mg/200 mg), IV infusion<br>* Other names: MK-4820A;|
| Active Comparator: Chemotherapy (Bendamustine or Gemcitabine)<br>Participants will receive physician's choice of EITHER bendamustine by IV infusion at a dose between 90 and 120 mg/m^2 on Day 1 and Day 2 of either a 3- or 4-week cycle for up to 6 cycles OR gemcitabine by IV infusion at a dose between 800 and 1200 mg/m^2 on Day 1 and Day 8 of a 3-week cycle for up to 6 cycles. | Drug: bendamustine<br>* IV infusion<br>* Other names: BENDEKA®;Drug: gemcitabine<br>* IV infusion<br>* Other names: GEMZAR®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) per Lugano Response Criteria as Assessed by Blinded Independent Central Review (BICR) | PFS is defined as the time from randomization to the first documented disease progression per Lugano criteria 2014 as assessed by BICR or death due to any cause, whichever occurs first. | Up to approximately 43 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from randomization to death due to any cause. | Up to approximately 105 months | 
| Objective Response Rate (ORR) per Lugano Response Criteria as Assessed by BICR | ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per Lugano criteria 2014 as assessed by BICR. | Up to approximately 25 months | 
| Duration of Response (DOR) per Lugano Response Criteria as Assessed by BICR | For participants who demonstrate CR or PR per Lugano criteria 2014 as assessed by BICR, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. | Up to approximately 43 months | 
| Number of Participants Who Experienced At Least One Adverse Event (AE) | An AE is any untoward medical occurrence in a clinical study participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be presented. | Up to approximately 27 months | 
| Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) | An AE is any untoward medical occurrence in a clinical study participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be presented. | Up to approximately 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)