A Study of Pembrolizumab/Vibostolimab (MK-7684A) in Relapsed/Refractory Hematological Malignancies (MK-7684A-004, KEYVIBE-004)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Hematological Malignancies

Treatments: Biological: Pembrolizumab/vibostolimab coformulation

Study type: Interventional

Funder types: Industry

Identifiers

NCT05005442

MK-7684A-004 (Other Identifier)

7684A-004

KEYVIBE-004 (Other Identifier)

2021-001700-15 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 192 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

- Have confirmed relapsed/refractory classic Hodgkins Lymphoma (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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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192 participants in 1 patient group

Pembrolizumab/vibostolimab coformulation

Experimental group

Description:

Participants will receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Treatment:

Biological: Pembrolizumab/vibostolimab coformulation