Clinical trial NCT05005442: A Study of Pembrolizumab/Vibostolimab (MK-7684A) in Relapsed/Refractory Hematological Malignancies (MK-7684A-004, KEYVIBE-004)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hematological Malignancies
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-08-13
Enrollment: 191
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with a Dose-Limiting Toxicity (DLT)
timeFrame: Up to approximately 6 weeks
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 27 months
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 24 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 24 months
measure: Lowest Plasma Concentration (Ctrough) of Vibostolimab
timeFrame: Predose at Cycles 1, 2, 4, 8, and every 12 weeks afterwards (up to ~2 years). Cycle = 3 weeks
measure: Maximum Concentration (Cmax) of Vibostolimab
timeFrame: Postdose: after end of infusion (up to ~10 minutes) at Cycles 1 and 8. Cycle = 3 weeks
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center-Hematology ( Site 0024)
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus-The Center for Cancer and Blood Disorders ( Site 0021
state: Colorado
city: Chicago
country: United States
facility: University of Chicago Medical Center ( Site 0005)
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Hospital ( Site 0003)
state: Michigan
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center ( Site 0004)
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey ( Site 0023)
state: New Jersey
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center ( Site 0014)
state: Texas
city: Spokane
country: United States
facility: Medical Oncology Associates, PS ( Site 0001)
state: Washington
city: Milwaukee
country: United States
facility: MEDICAL COLLEGE OF WISCONSIN ( Site 0016)
state: Wisconsin
city: Curitiba
country: Brazil
facility: Instituto do Câncer e Transplante de Curitiba ( Site 0611)
state: Parana
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 0601)
state: Rio Grande Do Norte
city: Vancouver
country: Canada
facility: BC Cancer Vancouver ( Site 0034)
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0031)
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital ( Site 0032)
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre ( Site 0037)
state: Quebec
city: Chile
country: Chile
facility: Instituto Nacional del Cancer ( Site 0626)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: FALP-UIDO ( Site 0623)
state: Region M. De Santiago
city: Copenhagen
country: Denmark
facility: Rigshospitalet-Hematology - CTU ( Site 0361)
state: Hovedstaden
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital, Skejby-Blodsygdomme ( Site 0362)
state: Midtjylland
city: Villejuif
country: France
facility: Gustave Roussy-DITEP ( Site 0301)
state: Paris
city: Pierre-Bénite
country: France
facility: centre hospitalier lyon sud-Service Hématologie ( Site 0300)
state: Rhone
city: Paris
country: France
facility: Pitie Salpetriere University Hospital-Clinical haematology ( Site 0304)
city: Marburg
country: Germany
facility: Universitätsklinikum Marburg ( Site 0333)
state: Hessen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen ( Site 0327)
state: Nordrhein-Westfalen
city: Köln
country: Germany
facility: Universitaetsklinikum Koeln-Klinik I für Innere Medizin ( Site 0321)
state: Nordrhein-Westfalen
city: Trier
country: Germany
facility: Klinikum Mutterhaus der Borromäerinnen-Innere Medizin I ( Site 0325)
state: Rheinland-Pfalz
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig ( Site 0328)
state: Sachsen
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf-II. medical clinic ( Site 0332)
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem Klinikai Központ-I.sz. Belgyógyászati Klinika Hematológia ( Site 0401)
state: Baranya
city: Budapest
country: Hungary
facility: Országos Onkológiai Intézet-HEMATOLÓGIA ÉS LYMPHOMA OSZTÁLY KEMOTERÁPIA A ( Site 0405)
state: Pest
city: Budapest
country: Hungary
facility: Semmelweis University-Belgyógyászati és Hematológiai Klinika ( Site 0403)
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont-Belgyógyászati Klinika (Haematologia) ( Site 0402)
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center-Hematology Department ( Site 0523)
city: Haifa
country: Israel
facility: Rambam Health Care Campus ( Site 0526)
city: Jerusalem
country: Israel
facility: Hadassah Medical Center ( Site 0522)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center-Hemato Oncology ( Site 0524)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 0525)
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli-ISTITUTO DI EMATOLOGIA ( Site 0383)
state: Lazio
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia-Hemathology ( Site 0400)
state: Lombardia
city: Milano
country: Italy
facility: Ospedale San Raffaele-Unità Linfomi ( Site 0382)
state: Lombardia
city: Bologna
country: Italy
facility: Policlinico S. Orsola- Malpighi-Istituto di Ematologia "L. e A. Seragnoli" ( Site 0381)
city: Wrocaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny-Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku ( Site
state: Dolnoslaskie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Chłonnego ( S
state: Mazowieckie
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0424)
state: Pomorskie
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0427)
state: Slaskie
city: Ufa
country: Russian Federation
facility: GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 0548)
state: Baskortostan, Respublika
city: Saint Petersburg
country: Russian Federation
facility: Almazov National Medical Research Centre-Intensive care unit No. 10 for oncohematological patients (
state: Leningradskaya Oblast
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital S.P. Botkin ( Site 0547)
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: Russian Scientific Research Institute of Hematology and Blood Transfusion-Hematology ( Site 0542)
state: Sankt-Peterburg
city: L'Hospitalet Del Llobregat
country: Spain
facility: Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 0442)
state: Barcelona
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra ( Site 0444)
state: Navarra
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology ( Site 0446)
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca-Hematology ( Site 0441)
city: Kaohsiung Niao Sung Dist
country: Taiwan
facility: Chang Gung Memorial Hospital at Kaohsiung ( Site 0263)
state: Kaohsiung
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation-Linkou Branch ( Site 0262)
city: Bornova
country: Turkey
facility: Ege University Medicine of Faculty ( Site 0565)
state: Izmir
city: Ankara
country: Turkey
facility: Ankara University Hospital Cebeci ( Site 0561)
city: Istanbul
country: Turkey
facility: Mega Medipol-Hematology ( Site 0567)
city: Istanbul
country: Turkey
facility: Vehbi Koc Vakfi - Amerikan Hastanesi ( Site 0562)
city: Izmir
country: Turkey
facility: Dokuz Eylül Üniversitesi-Hematology ( Site 0563)
city: Samsun
country: Turkey
facility: Ondokuz Mayıs Universitesi ( Site 0564)
city: Cherkassy
country: Ukraine
facility: Cherkasy Regional Oncology Dispensary ( Site 0593)
state: Cherkaska Oblast
city: Kyiv
country: Ukraine
facility: National Cancer Institute ( Site 0585)
state: Kyivska Oblast
city: Lviv
country: Ukraine
facility: Institute of Transfusion Medicine and Blood of the National Academy of Medical Sciences of Ukraine (
state: Lvivska Oblast
city: Kyiv
country: Ukraine
facility: National Research Center for Radiation Medicine of National Academy of Medical Sciences of Ukraine (
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: