A Study of Pembrolizumab/Vibostolimab (MK-7684A) in Relapsed/Refractory Hematological Malignancies (MK-7684A-004, KEYVIBE-004)
- Interventional
- Recruiting
- NCT05005442
Contact Information
A Phase 2, Open-label Study to Evaluate the Safety and Efficacy of MK-7684A (MK-7684 [Vibostolimab] With MK-3475 [Pembrolizumab] Coformulation) in Participants With Relapsed or Refractory Hematological Malignancies
The purpose of the study is to determine the safety and tolerability of pembrolizumab/vibostolimab (MK-7684A) in hematological malignancies. This study will also evaluate the overall response rate (ORR), the duration of response (DOR), and disease control rate (DCR) following administration of pembrolizumab/vibostolimab. In addition, this study will characterize pharmacokinetic (PK) profile of vibostolimab (MK-7684).
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers?
No
Inclusion Criteria
- Have confirmed relapsed/refractory classic Hodgkins Lyphoma (cHL), Primary mediastinal B-cell lymphoma (PMBCL), Follicular Lymphoma (FL), Diffuse large B-cell lymphoma (DLBCL) or Non-Hodgkins Lymphoma (NHL), or multiple myeloma (MM).
For PMBCL, DLBCL, FL, and MM:
- Must be relapsed or refractory to CAR-T-cell therapy or unable to receive it.
For DLBCL and NHL:
- Must have exhausted or be ineligible for or intolerant to all treatments, which in the opinion of the investigator are standard of care for their disease.
For NHL:
- Participants with Mantle cell lymphoma (MCL) must have received prior Bruton's tyrosine kinase inhibitor therapy.
All participants:
- Have measurable disease.
- Have adequate organ function.
- Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before allocation.
- Must be able to provide newly obtained bone marrow biopsy or aspirate material for disease assessment.
- Female participants are eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of non child-bearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle.
Exclusion Criteria
For DLBCL and NHL:
- Has lymphoplasmacytic lymphomas, Waldenstrom's macroglobulinemia, chronic lymphocytic leukemia (not associated with small lymphocytic lymphoma), Burkitt (-like) lymphoma, mature T cell and NK cell neoplasms, immunodeficiency associated lymphoproliferative neoplasms, or histiocytic and dendritic cell neoplasms.
For MM:
- Has oligo-secretory myeloma, plasma cell leukemia, smoldering multiple myeloma, or monoclonal gammopathy of undetermined significance.
- Has a history of primary amyloidosis, hyperviscosity or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
- Has known prior or current central nervous system (CNS) involvement.
For Epstein Barr virus (EBV) positive DLBCL:
- Associated with a solid organ transplant.
For all participants:
- A WOCBP who has a positive urine pregnancy test within 72 hours before study intervention allocation.
- Has clinically significant cardiovascular disease within 12 months from first dose of study intervention.
- Has a history of a second malignancy.
- Any PMBCL participants that require the use of urgent cytoreductive therapy.
- If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery before starting study intervention.
- Has received prior radiotherapy within 2 weeks of start of study intervention.
- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
- Has a known severe hypersensitivity to MK-7684A, vibostolimab or pembrolizumab and/or any of its excipients.
- Has a known history of Human Immunodeficiency Virus (HIV) infection.
- Has an active autoimmune disease that has required systemic treatment in past 2 years.
- Has an active infection requiring systemic therapy.
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
- Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks before enrollment.
- Has dual active HBV infection (HBsAg (+) and /or detectable HBV DNA) and Hepatitis C (HCV) infection (anti-HCV Ab (+) and detectable HCV RNA) at study entry..
- Has had an allogenic hematopoietic stem cell/solid organ transplantation within the last 5 years.
- Have confirmed relapsed/refractory classic Hodgkins Lyphoma (cHL), Primary mediastinal B-cell lymphoma (PMBCL), Follicular Lymphoma (FL), Diffuse large B-cell lymphoma (DLBCL) or Non-Hodgkins Lymphoma (NHL), or multiple myeloma (MM).
For PMBCL, DLBCL, FL, and MM:
- Must be relapsed or refractory to CAR-T-cell therapy or unable to receive it.
For DLBCL and NHL:
- Must have exhausted or be ineligible for or intolerant to all treatments, which in the opinion of the investigator are standard of care for their disease.
For NHL:
- Participants with Mantle cell lymphoma (MCL) must have received prior Bruton's tyrosine kinase inhibitor therapy.
All participants:
- Have measurable disease.
- Have adequate organ function.
- Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before allocation.
- Must be able to provide newly obtained bone marrow biopsy or aspirate material for disease assessment.
- Female participants are eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of non child-bearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle.
Exclusion Criteria
For DLBCL and NHL:
- Has lymphoplasmacytic lymphomas, Waldenstrom's macroglobulinemia, chronic lymphocytic leukemia (not associated with small lymphocytic lymphoma), Burkitt (-like) lymphoma, mature T cell and NK cell neoplasms, immunodeficiency associated lymphoproliferative neoplasms, or histiocytic and dendritic cell neoplasms.
For MM:
- Has oligo-secretory myeloma, plasma cell leukemia, smoldering multiple myeloma, or monoclonal gammopathy of undetermined significance.
- Has a history of primary amyloidosis, hyperviscosity or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
- Has known prior or current central nervous system (CNS) involvement.
For Epstein Barr virus (EBV) positive DLBCL:
- Associated with a solid organ transplant.
For all participants:
- A WOCBP who has a positive urine pregnancy test within 72 hours before study intervention allocation.
- Has clinically significant cardiovascular disease within 12 months from first dose of study intervention.
- Has a history of a second malignancy.
- Any PMBCL participants that require the use of urgent cytoreductive therapy.
- If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery before starting study intervention.
- Has received prior radiotherapy within 2 weeks of start of study intervention.
- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
- Has a known severe hypersensitivity to MK-7684A, vibostolimab or pembrolizumab and/or any of its excipients.
- Has a known history of Human Immunodeficiency Virus (HIV) infection.
- Has an active autoimmune disease that has required systemic treatment in past 2 years.
- Has an active infection requiring systemic therapy.
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
- Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks before enrollment.
- Has dual active HBV infection (HBsAg (+) and /or detectable HBV DNA) and Hepatitis C (HCV) infection (anti-HCV Ab (+) and detectable HCV RNA) at study entry..
- Has had an allogenic hematopoietic stem cell/solid organ transplantation within the last 5 years.