A Study of Pembrolizumab/Vibostolimab (MK-7684A) in Relapsed/Refractory Hematological Malignancies (MK-7684A-004, KEYVIBE-004)
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 |
---|---|---|
|
Phase 2 |
Study Design
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:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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
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.- 7684A-004
- MK-7684A-004
- KEYVIBE-004
- 2021-001700-15