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

Hematological Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05005442
• Other study ID #: 7684A-004
• Secondary ID: MK-7684A-004KEYV
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 28, 2021
• Est. completion date: August 29, 2024

Study information

• Verified date: August 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 180
• Est. completion date: August 29, 2024
• Est. primary completion date: August 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancies
• Neoplasms

Intervention

Biological:
• Pembrolizumab/vibostolimab coformuation
Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion Q3W up to approximately 2 years.

Locations

Country	Name	City	State
Brazil	Instituto do Câncer e Transplante de Curitiba ( Site 0611)	Curitiba	Parana
Brazil	Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 0601)	Natal	Rio Grande Do Norte
Canada	Jewish General Hospital ( Site 0032)	Montreal	Quebec
Canada	McGill University Health Centre ( Site 0037)	Montréal	Quebec
Canada	Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0031)	Toronto	Ontario
Canada	BC Cancer Vancouver ( Site 0034)	Vancouver	British Columbia
Chile	Instituto Nacional del Cancer ( Site 0626)	Chile	Region M. De Santiago
Chile	FALP-UIDO ( Site 0623)	Santiago	Region M. De Santiago
Denmark	Aarhus Universitetshospital, Skejby-Blodsygdomme ( Site 0362)	Aarhus	Midtjylland
Denmark	Rigshospitalet-Hematology - CTU ( Site 0361)	Copenhagen	Hovedstaden
France	Pitie Salpetriere University Hospital-Clinical haematology ( Site 0304)	Paris
France	centre hospitalier lyon sud-Service Hématologie ( Site 0300)	Pierre-Bénite	Rhone
France	Gustave Roussy-DITEP ( Site 0301)	Villejuif	Paris
Germany	Universitaetsklinikum Essen ( Site 0327)	Essen	Nordrhein-Westfalen
Germany	Universitaetsklinikum Hamburg-Eppendorf-II. medical clinic ( Site 0332)	Hamburg
Germany	Universitaetsklinikum Koeln-Klinik I für Innere Medizin ( Site 0321)	Köln	Nordrhein-Westfalen
Germany	Universitätsklinikum Leipzig ( Site 0328)	Leipzig	Sachsen
Germany	Universitätsklinikum Marburg ( Site 0333)	Marburg	Hessen
Germany	Klinikum Mutterhaus der Borromäerinnen-Innere Medizin I ( Site 0325)	Trier	Rheinland-Pfalz
Hungary	Országos Onkológiai Intézet-HEMATOLÓGIA ÉS LYMPHOMA OSZTÁLY KEMOTERÁPIA A ( Site 0405)	Budapest	Pest
Hungary	Semmelweis University-Belgyógyászati és Hematológiai Klinika ( Site 0403)	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont-Belgyógyászati Klinika (Haematologia) ( Site 0402)	Debrecen
Hungary	Pécsi Tudományegyetem Klinikai Központ-I.sz. Belgyógyászati Klinika Hematológia ( Site 0401)	Pécs	Baranya
Israel	Soroka Medical Center-Hematology Department ( Site 0523)	Be'er Sheva
Israel	Rambam Health Care Campus ( Site 0526)	Haifa
Israel	Hadassah Medical Center ( Site 0522)	Jerusalem
Israel	Sheba Medical Center-Hemato Oncology ( Site 0524)	Ramat Gan
Israel	Sourasky Medical Center ( Site 0525)	Tel Aviv
Italy	Policlinico S. Orsola- Malpighi-Istituto di Ematologia "L. e A. Seragnoli" ( Site 0381)	Bologna
Italy	Azienda Ospedaliera Spedali Civili di Brescia-Hemathology ( Site 0400)	Brescia	Lombardia
Italy	Ospedale San Raffaele-Unità Linfomi ( Site 0382)	Milano	Lombardia
Italy	Fondazione Policlinico Universitario Agostino Gemelli-ISTITUTO DI EMATOLOGIA ( Site 0383)	Roma	Lazio
Poland	Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0424)	Gdansk	Pomorskie
Poland	Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0427)	Gliwice	Slaskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Ukladu Chlonnego ( S	Warszawa	Mazowieckie
Poland	Uniwersytecki Szpital Kliniczny-Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku ( Site	Wrocaw	Dolnoslaskie
Russian Federation	Moscow City Clinical Hospital S.P. Botkin ( Site 0547)	Moscow	Moskva
Russian Federation	Almazov National Medical Research Centre-Intensive care unit No. 10 for oncohematological patients (	Saint Petersburg	Leningradskaya Oblast
Russian Federation	Russian Scientific Research Institute of Hematology and Blood Transfusion-Hematology ( Site 0542)	Saint Petersburg	Sankt-Peterburg
Russian Federation	GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 0548)	Ufa	Baskortostan, Respublika
Spain	Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 0442)	L'Hospitalet Del Llobregat	Barcelona
Spain	Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology ( Site 0446)	Madrid
Spain	Clinica Universidad de Navarra ( Site 0444)	Pamplona	Navarra
Spain	Hospital Universitario de Salamanca-Hematology ( Site 0441)	Salamanca
Taiwan	Chang Gung Memorial Hospital at Kaohsiung ( Site 0263)	Kaohsiung Niao Sung Dist	Kaohsiung
Taiwan	Chang Gung Medical Foundation-Linkou Branch ( Site 0262)	Taoyuan
Turkey	Ankara University Hospital Cebeci ( Site 0561)	Ankara
Turkey	Ege University Medicine of Faculty ( Site 0565)	Bornova	Izmir
Turkey	Mega Medipol-Hematology ( Site 0567)	Istanbul
Turkey	Vehbi Koc Vakfi - Amerikan Hastanesi ( Site 0562)	Istanbul
Turkey	Dokuz Eylül Üniversitesi-Hematology ( Site 0563)	Izmir
Turkey	Ondokuz Mayis Universitesi ( Site 0564)	Samsun
Ukraine	Cherkasy Regional Oncology Dispensary ( Site 0593)	Cherkassy	Cherkaska Oblast
Ukraine	National Cancer Institute ( Site 0585)	Kyiv	Kyivska Oblast
Ukraine	National Research Center for Radiation Medicine of National Academy of Medical Sciences of Ukraine (	Kyiv
Ukraine	Institute of Transfusion Medicine and Blood of the National Academy of Medical Sciences of Ukraine (	Lviv	Lvivska Oblast
United States	University of Colorado Anschutz Medical Campus-The Center for Cancer and Blood Disorders ( Site 0021	Aurora	Colorado
United States	University of Chicago Medical Center ( Site 0005)	Chicago	Illinois
United States	Henry Ford Hospital ( Site 0003)	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center-Hematology ( Site 0024)	Duarte	California
United States	John Theurer Cancer Center at Hackensack University Medical Center ( Site 0004)	Hackensack	New Jersey
United States	University of Texas MD Anderson Cancer Center ( Site 0014)	Houston	Texas
United States	MEDICAL COLLEGE OF WISCONSIN ( Site 0016)	Milwaukee	Wisconsin
United States	Rutgers Cancer Institute of New Jersey ( Site 0023)	New Brunswick	New Jersey
United States	Medical Oncology Associates, PS ( Site 0001)	Spokane	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Chile,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Poland,  Russian Federation,  Spain,  Taiwan,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with a Dose-Limiting Toxicity (DLT)	A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Number of participants who experience a DLT per CTCAE 5.0 will be reported.	Up to approximately 6 weeks
Primary	Number of Participants Who Experienced an Adverse Event (AE)	An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants who experience an AE will be reported.	Up to approximately 27 months
Primary	Number of Participants Who Discontinued Study Treatment Due to an AE	An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants discontinued from the study treatment due to an AE will be reported.	Up to approximately 24 months
Secondary	Objective Response Rate (ORR)	ORR is defined as the percentage of participants who have a response as defined by the specific disease criteria of the hematological malignancy. The percentage of participants who experience a response will be presented.	Up to approximately 24 months
Secondary	Duration of Response (DOR)	DOR is the time from response (R) to progression/death (P/D). The DOR will be presented.	Up to approximately 24 months
Secondary	Disease Control Rate (DCR)	DCR is defined as the percentage of participants who have a Complete Response (CR), a Partial Response (PR), or Stable Disease (SD). The percentage of participants who experience a CR, a PR, or SD will be presented.	Up to approximately 24 months
Secondary	Lowest Plasma Concentration (Ctrough) of Vibostolimab	Ctrough is the lowest concentration reached by a drug before the next dose is administered. Blood samples collected predose will be used to determine Ctrough of Vibostolimab.	Predose at Cycles 1, 2, 4, 8, and every 12 weeks afterwards (up to ~2 years). Cycle = 3 weeks
Secondary	Maximum Concentration (Cmax) of Vibostolimab	Cmax is the maximum concentration of the drug observed in plasma. Blood samples collected post dose will be used to determine Cmax of Vibostolimab.	Postdose: after end of infusion (up to ~10 minutes) at Cycles 1 and 8. Cycle = 3 weeks

External Links

•   Merck Clinical Trials Information