Hodgkin Lymphoma
Conditions
Keywords
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)
Brief summary
Researchers are looking for a way to treat classical Hodgkin lymphoma (cHL) that is relapsed (the cancer has come back after treatment) or refractory (current treatment has stopped working to slow or stop cancer growth). Researchers want to learn if people who receive coformulated favezelimab/pembrolizumab (MK-4280A) live longer without the cancer getting worse compared to those who receive chemotherapy.
Interventions
BIOLOGICALfavezelimab/pembrolizumab
Coformulated favezelimab/pembrolizumab (800 mg/200 mg), IV infusion
DRUGbendamustine
IV infusion
DRUGgemcitabine
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Per Lugano Response Criteria as Assessed by Investigator | Up to approximately 34 months | PFS was defined as the time from randomization to the first documented disease progression per Lugano criteria 2014 as assessed by investigator or death due to any cause, whichever occurred first. Progressive disease was defined as uptake moderately or markedly higher than the liver with an increase in overall uptake compared with nadir, and/or the appearance of new lesions consistent with lymphoma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 34 months | OS was defined as the time from randomization to death due to any cause. |
| Objective Response Rate (ORR) Per Lugano Response Criteria as Assessed by Investigator | Up to approximately 34 months | ORR was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) per Lugano criteria 2014 as assessed by investigator. CR or PR were evaluated using computed tomography (CT) and metabolic imaging (fluorodeoxyglucose-positron emission tomography (FDG-PET)). CR is complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \>50% in length beyond normal). |
| Duration of Response (DOR) Per Lugano Response Criteria as Assessed by Investigator | Up to approximately 34 months | For participants who demonstrated CR or PR per Lugano criteria 2014 as assessed by investigator, DOR was defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurred first. CR or PR were evaluated using computed tomography (CT) and metabolic imaging (fluorodeoxyglucose-positron emission tomography (FDG-PET)). CR is complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \>50% in length beyond normal). |
| Number of Participants Who Experienced At Least One Adverse Event (AE) | Up to approximately 28 months | An AE was 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 experienced an AE is presented. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 28 months | An AE was 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 discontinued study treatment due to an AE is presented. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Czechia, France, Germany, Israel, Mexico, Poland, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Recruitment details
Participants with programmed cell death 1 (PD-1) protein- or programmed cell death ligand 1 (PD-L1) \[PD-(L)1\]-refractory, relapsed or refractory classical Hodgkin lymphoma were recruited to receive the coformulation favezelimab/pembrolizumab (MK-4280A) or physician's choice chemotherapy (gemcitabine or bendamustine).
Pre-assignment details
Participants were randomized 1:1 to receive favezelimab/pembrolizumab or physician's choice chemotherapy (gemcitabine or bendamustine). Participants assigned to gemcitabine or bendamustine could cross over to favezelimab/pembrolizumab if crossover phase criteria were met. Per protocol, response/progression or adverse events (AEs) that occurred after the switchover to favezelimab/pembrolizumab were not counted towards efficacy outcome measures or safety outcome measures, respectively.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 44.7 Years STANDARD_DEVIATION 17.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 74 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Prior Autologous Stem Cell Transplant Status (auto-SCT) No | 96 Participants |
| Prior Autologous Stem Cell Transplant Status (auto-SCT) Yes | 107 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 28 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 159 Participants |
| Sex/Gender, Customized Female | 45 Participants |
| Sex/Gender, Customized Male | 58 Participants |
| Sex/Gender, Customized Undifferentiated | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 15 / 104 | 14 / 99 | 7 / 52 |
| other Total, other adverse events | 93 / 104 | 85 / 97 | 41 / 52 |
| serious Total, serious adverse events | 25 / 104 | 27 / 97 | 9 / 52 |
Outcome results
None listed