A randomized clinical phase 3 study of MK-4280A (co-formulated Favezelimab [MK-4280] plus Pembrolizumab [MK-3475]) compared to physician's choice chemotherapy in patients with PD(L)1-refractory, relapsed or refractory classical Hodgkin lymphoma (KEYFORM-008)
Summary description of the study
The standard first-line treatment for cHL consists of chemotherapy with or without radiation, which has been shown to lead to long-term suppression of the disease in 60 to 80% of patients. However, 20 to 40% of patients experience a recurrence of the disease after first-line chemotherapy. Recently, significant progress has been made in the treatment of relapsed/refractory cHL through immunotherapies (such as anti-PD-1 antibodies like Pembrolizumab), and the relapse rate has been significantly reduced. However, for patients who still experience a relapse, there are no further standard treatment options available. This study investigates the safety, tolerability, pharmacokinetics, and efficacy of MK-4280A (MK-4280 combined with Pembrolizumab) compared to conventional chemotherapy. "Pharmacokinetics" refers to the absorption, metabolism, and elimination of the substance in the body. Approximately 360 patients are expected to participate in this study worldwide.
(BASEC)
Intervention under investigation
These are the investigational products of the study:
MK-4280A consists of Pembrolizumab plus MK-4280, making it a co-formulation of two agents.
o Pembrolizumab: The immune system plays an important role in controlling tumors. Tumors produce ligands that bind to receptors on immune cells, preventing the tumor from being recognized by the immune system. Pembrolizumab is an antibody that binds to one of these receptors (PD1 receptor) and inactivates it. This enhances the body's ability to combat the tumor through the immune system. Pembrolizumab is already approved in Switzerland and other countries for the treatment of various cancers, including cHL.
o MK-4280 is an antibody that increases the activity of specific immune cells (called T-cells) and thus also enhances the body's ability to combat the tumor. MK-4280 is an experimental drug also known as Favezelimab. It has not yet been approved for sale.
The chemotherapies that can be used in this study are Bendamustine or Gemcitabine. These are commonly used treatments for patients with this cancer.
After careful eligibility assessment, medical history collection, and detailed explanation, the participant will be included in the study. The participant will then be assigned to one of the following two groups:
Group A: Receives the drug MK-4280A
Group B: Receives chemotherapy (Bendamustine or Gemcitabine)
Participants assigned to Group B (chemotherapy) may potentially switch to Group A (MK-4280A) if their cancer worsens.
This study is an open-label study, meaning that both the physician and the participants themselves know which treatment they have been assigned.
The treatment duration with MK-4280A is approximately 2 years, as long as safety is ensured and the medication shows efficacy. Participants will visit the study center approximately 38 times during the treatment period. For patients receiving chemotherapy, the treatment duration is approximately 5-6 months, during which they will visit the study center approximately 12 times. During and after the treatment phase, health status will be regularly monitored for any potential disease progression. In the event of disease worsening, participants will visit the study center at least one more time for a safety follow-up visit. Subsequently, participants will be contacted by phone approximately every 12 weeks.
During study visits, various measures and examinations may be conducted, including: discussion of well-being and current medication, questioning about daily activities and any related restrictions, administration/dispensing of study medication, imaging procedures such as PET, CT, and/or MRI scans, cardiac examinations (electrocardiogram (ECG), samples of blood, urine, bone marrow, or tissue, physical examination including checking vital signs (pulse, blood pressure, etc.).
(BASEC)
Disease under investigation
Classical Hodgkin lymphoma (cHL) is a subgroup of lymph node cancer that can be determined by the presence of certain cell types and markers. In this study, participants with classical Hodgkin lymphoma (cHL) will be examined who have not responded or no longer respond to all approved treatments or who have experienced a recurrence after treatment with PD-(L)1 antibodies. This is referred to as relapsed or refractory cHL (R/R cHL). For cancer patients who experience a relapse despite initial treatment with approved therapeutic options, there are often limited possibilities to alleviate their suffering. This study investigates whether a new combination of immunotherapy can provide advantages over conventional chemotherapy.
(BASEC)
• Histologically confirmed diagnosis of classical Hodgkin lymphoma with at least one nodal lesion • Experienced relapse or refractory cHL where all available treatment options with known clinical benefit have been exhausted. • Disease progression occurred during treatment with an anti-PD-(L)1 antibody (BASEC)
Exclusion criteria
• Severe hypersensitivity to Pembrolizumab, Favezelimab, and/or any of their other components. • History of a serious adverse event after prior checkpoint inhibitor therapy. • Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy. • History of CNS metastases or active CNS involvement. (BASEC)
Trial sites
Bellinzona
(BASEC)
Sponsor
MSD Merck Sharp & Dohme AG, Luzern
(BASEC)
Contact
Contact Person Switzerland
Klaudia Georgi
+41 58 618 33 88
klaudia.georgi@cluttermsd.comMSD Merck Sharp & Dohme AG, Luzern
(BASEC)
General Information
Merck Sharp & Dohme LLC
(ICTRP)
Scientific Information
Merck Sharp & Dohme LLC
(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Ticino
(BASEC)
Date of authorisation
06.10.2023
(BASEC)
ICTRP Trial ID
NCT05508867 (ICTRP)
Official title (approved by ethics committee)
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) (BASEC)
Academic title
A Phase 2 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) (ICTRP)
Public title
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) (ICTRP)
Disease under investigation
Hodgkin Lymphoma (ICTRP)
Intervention under investigation
Biological: favezelimab/pembrolizumabDrug: bendamustineDrug: gemcitabine (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Inclusion/Exclusion criteria
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. (ICTRP)
not available
Primary and secondary end points
Progression Free Survival (PFS) per Lugano Response Criteria as Assessed by investigator (ICTRP)
Overall Survival (OS);Objective Response Rate (ORR) per Lugano Response Criteria as Assessed by investigator;Duration of Response (DOR) per Lugano Response Criteria as Assessed by investigator;Number of Participants Who Experienced At Least One Adverse Event (AE);Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) (ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Medical Director, Merck Sharp & Dohme LLC (ICTRP)
Secondary trial IDs
MK-4280A-008, 2023-503615-14-00, U1111-1287-5864, 2022-000371-39, 4280A-008 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT05508867 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available