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

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05005442
Collaborator
(none)
180
61
1
35.4
3
0.1

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
  • Biological: Pembrolizumab/vibostolimab coformuation
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
180 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 28, 2021
Anticipated Primary Completion Date :
Sep 9, 2024
Anticipated Study Completion Date :
Sep 9, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pembrolizumab/vibostolimab coformulation

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.

Biological: Pembrolizumab/vibostolimab coformuation
Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion Q3W up to approximately 2 years.
Other Names:
  • MK7684A
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants with a Dose-Limiting Toxicity (DLT) [Up to approximately 6 weeks]

      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.

    2. Number of Participants Who Experienced an Adverse Event (AE) [Up to approximately 27 months]

      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.

    3. Number of Participants Who Discontinued Study Treatment Due to an AE [Up to approximately 24 months]

      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.

    Secondary Outcome Measures

    1. Objective Response Rate (ORR) [Up to approximately 24 months]

      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.

    2. Duration of Response (DOR) [Up to approximately 24 months]

      DOR is the time from response (R) to progression/death (P/D). The DOR will be presented.

    3. Disease Control Rate (DCR) [Up to approximately 24 months]

      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.

    4. Lowest Plasma Concentration (Ctrough) of Vibostolimab [Predose at Cycles 1, 2, 4, 8, and every 12 weeks afterwards (up to ~2 years). Cycle = 3 weeks]

      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.

    5. Maximum Concentration (Cmax) of Vibostolimab [Postdose: after end of infusion (up to ~10 minutes) at Cycles 1 and 8. Cycle = 3 weeks]

      Cmax is the maximum concentration of the drug observed in plasma. Blood samples collected post dose will be used to determine Cmax of Vibostolimab.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Comprehensive Cancer Center-Hematology ( Site 0024) Duarte California United States 91010
    2 University of Colorado Anschutz Medical Campus-The Center for Cancer and Blood Disorders ( Site 0021 Aurora Colorado United States 80045
    3 University of Chicago Medical Center ( Site 0005) Chicago Illinois United States 60637
    4 Henry Ford Hospital ( Site 0003) Detroit Michigan United States 48202
    5 John Theurer Cancer Center at Hackensack University Medical Center ( Site 0004) Hackensack New Jersey United States 07601
    6 Rutgers Cancer Institute of New Jersey ( Site 0023) New Brunswick New Jersey United States 08901
    7 University of Texas MD Anderson Cancer Center ( Site 0014) Houston Texas United States 77030
    8 Medical Oncology Associates, PS ( Site 0001) Spokane Washington United States 99208
    9 MEDICAL COLLEGE OF WISCONSIN ( Site 0016) Milwaukee Wisconsin United States 53226
    10 Instituto do Câncer e Transplante de Curitiba ( Site 0611) Curitiba Parana Brazil 80510130
    11 Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 0601) Natal Rio Grande Do Norte Brazil 59075-740
    12 BC Cancer Vancouver ( Site 0034) Vancouver British Columbia Canada V5Z 4E6
    13 Jewish General Hospital ( Site 0032) Montreal Quebec Canada H3T 1E2
    14 McGill University Health Centre ( Site 0037) Montréal Quebec Canada H4A 3J1
    15 Instituto Nacional del Cancer ( Site 0626) Chile Region M. De Santiago Chile 8380455
    16 FALP-UIDO ( Site 0623) Santiago Region M. De Santiago Chile 6900941
    17 Rigshospitalet-Hematology - CTU ( Site 0361) Copenhagen Hovedstaden Denmark 2100
    18 Aarhus Universitetshospital, Skejby-Blodsygdomme ( Site 0362) Aarhus Midtjylland Denmark 8200
    19 Gustave Roussy-DITEP ( Site 0301) Villejuif Paris France 94800
    20 centre hospitalier lyon sud-Service Hématologie ( Site 0300) Pierre-Bénite Rhone France 69310
    21 Pitie Salpetriere University Hospital-Clinical haematology ( Site 0304) Paris France 75013
    22 Universitätsklinikum Marburg ( Site 0333) Marburg Hessen Germany 35033
    23 Universitaetsklinikum Essen ( Site 0327) Essen Nordrhein-Westfalen Germany 45122
    24 Klinikum Mutterhaus der Borromäerinnen-Innere Medizin I ( Site 0325) Trier Rheinland-Pfalz Germany 54290
    25 Universitätsklinikum Leipzig ( Site 0328) Leipzig Sachsen Germany 04103
    26 Universitaetsklinikum Hamburg-Eppendorf-II. medical clinic ( Site 0332) Hamburg Germany 20246
    27 Pécsi Tudományegyetem Klinikai Központ-I.sz. Belgyógyászati Klinika Hematológia ( Site 0401) Pécs Baranya Hungary 7624
    28 Országos Onkológiai Intézet-HEMATOLÓGIA ÉS LYMPHOMA OSZTÁLY KEMOTERÁPIA A ( Site 0405) Budapest Pest Hungary 1122
    29 Semmelweis University-Belgyógyászati és Hematológiai Klinika ( Site 0403) Budapest Hungary 1088
    30 Debreceni Egyetem Klinikai Kozpont-Belgyógyászati Klinika (Haematologia) ( Site 0402) Debrecen Hungary 4032
    31 Soroka Medical Center-Hematology Department ( Site 0523) Be'er Sheva Israel 8410101
    32 Rambam Health Care Campus ( Site 0526) Haifa Israel 3109601
    33 Hadassah Medical Center ( Site 0522) Jerusalem Israel 9112001
    34 Sheba Medical Center-Hemato Oncology ( Site 0524) Ramat Gan Israel 5262100
    35 Sourasky Medical Center ( Site 0525) Tel Aviv Israel 6423906
    36 Fondazione Policlinico Universitario Agostino Gemelli-ISTITUTO DI EMATOLOGIA ( Site 0383) Roma Lazio Italy 00168
    37 Azienda Ospedaliera Spedali Civili di Brescia-Hemathology ( Site 0400) Brescia Lombardia Italy 25123
    38 Policlinico S. Orsola- Malpighi-Istituto di Ematologia "L. e A. Seragnoli" ( Site 0381) Bologna Italy 40138
    39 Ospedale San Raffaele-Unità Linfomi ( Site 0382) Milano Italy 20132
    40 Uniwersytecki Szpital Kliniczny-Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku ( Site Wrocaw Dolnoslaskie Poland 50-556
    41 Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Chłonnego ( S Warszawa Mazowieckie Poland 02-781
    42 Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0424) Gdańsk Pomorskie Poland 80-952
    43 Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0427) Gliwice Slaskie Poland 44-101
    44 GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 0548) Ufa Baskortostan, Respublika Russian Federation 450054
    45 Almazov National Medical Research Centre-Intensive care unit No. 10 for oncohematological patients ( Saint Petersburg Leningradskaya Oblast Russian Federation 197341
    46 Moscow City Clinical Hospital S.P. Botkin-Hematology ( Site 0547) Moscow Moskva Russian Federation 125284
    47 Russian Scientific Research Institute of Hematology and Blood Transfusion-Hematology ( Site 0542) Saint Petersburg Sankt-Peterburg Russian Federation 191024
    48 Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 0442) L'Hospitalet Del Llobregat Barcelona Spain 08908
    49 Clinica Universidad de Navarra ( Site 0444) Pamplona Navarra Spain 31008
    50 Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology ( Site 0446) Madrid Spain 28040
    51 Hospital Universitario de Salamanca-Hematology ( Site 0441) Salamanca Spain 37007
    52 Chang Gung Memorial Hospital at Kaohsiung ( Site 0263) Kaohsiung Niao Sung Dist Kaohsiung Taiwan 83301
    53 Chang Gung Medical Foundation-Linkou Branch ( Site 0262) Taoyuan Taiwan 333
    54 Ankara University Hospital Cebeci ( Site 0561) Ankara Turkey 06100
    55 Vehbi Koc Vakfi - Amerikan Hastanesi ( Site 0562) Istanbul Turkey 34365
    56 Dokuz Eylül Üniversitesi-Hematology ( Site 0563) Izmir Turkey 35340
    57 Ondokuz Mayıs Universitesi ( Site 0564) Samsun Turkey 55210
    58 Cherkasy Regional Oncology Dispensary ( Site 0593) Cherkassy Cherkaska Oblast Ukraine 18009
    59 National Cancer Institute ( Site 0585) Kyiv Kyivska Oblast Ukraine 03022
    60 Institute of Transfusion Medicine and Blood of the National Academy of Medical Sciences of Ukraine ( Lviv Lvivska Oblast Ukraine 79044
    61 National Research Center for Radiation Medicine of National Academy of Medical Sciences of Ukraine ( Kyiv Ukraine

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT05005442
    Other Study ID Numbers:
    • 7684A-004
    • MK-7684A-004
    • KEYVIBE-004
    • 2021-001700-15
    First Posted:
    Aug 13, 2021
    Last Update Posted:
    Aug 2, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 2, 2022