- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04152863
Efficacy, Safety, and Tolerability of Gebasaxturev (V937) Administered Intravenously or Intratumorally With Pembrolizumab (MK-3475) Versus Pembrolizumab Alone in Participants With Advanced/Metastatic Melanoma (V937-011)
March 1, 2024 updated by: Merck Sharp & Dohme LLC
A Phase 2, Randomized Clinical Study of Intravenous or Intratumoral Administration of V937 in Combination With Pembrolizumab (MK-3475) Versus Pembrolizumab Alone in Participants With Advanced/Metastatic Melanoma
This is a Phase 2 study to assess the efficacy, safety, and tolerability of gebasaxturev administered both intratumorally (ITu) and intravenously (IV) as combination therapy with pembrolizumab (MK-3475) versus pembrolizumab alone in anti-programmed cell death ligand 1 (anti-PD-L1)-treatment-naive participants with advanced/metastatic melanoma.
The primary hypothesis of the study is that gebasaxturev administered either ITu or IV in combination with pembrolizumab results in a superior objective response rate (ORR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review (BICR), compared to pembrolizumab alone.
This study will be terminated once all participants finish treatment with V937.
Participants eligible to continue to receive pembrolizumab will be transferred to MK-3475-587 study.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
85
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
South Australia
-
Woodville, South Australia, Australia, 5011
- The Queen Elizabeth Hospital ( Site 0143)
-
-
Victoria
-
Melbourne, Victoria, Australia, 3004
- Alfred Health ( Site 0142)
-
-
Western Australia
-
Murdoch, Western Australia, Australia, 6150
- Fiona Stanley Hospital ( Site 0141)
-
-
-
-
Region M. De Santiago
-
Santiago, Region M. De Santiago, Chile, 6900941
- FALP-UIDO ( Site 2062)
-
Santiago, Region M. De Santiago, Chile, 8420383
- Bradfordhill-Clinical Area ( Site 2061)
-
-
-
-
Cote-d Or
-
Dijon, Cote-d Or, France, 21079
- Centre Georges Francois Leclerc ( Site 2025)
-
-
Isere
-
La Tronche, Isere, France, 38700
- CHU de Grenoble Hopital Nord ( Site 2027)
-
-
-
-
Baden-Wurttemberg
-
Tübingen, Baden-Wurttemberg, Germany, 72076
- Universitaetsklinikum Tuebingen-Hautklinik ( Site 2001)
-
-
Bayern
-
Regensburg, Bayern, Germany, 93053
- Universitaetsklinikum Regensburg ( Site 2007)
-
-
Sachsen
-
Leipzig, Sachsen, Germany, 04103
- Universitaetsklinikum Leipzig AOeR ( Site 2005)
-
-
-
-
-
Haifa, Israel, 3109601
- Rambam Health Care Campus-Oncology Division ( Site 0040)
-
Jerusalem, Israel, 9112001
- Hadassah Ein Kerem Medical Center ( Site 0042)
-
Ramat Gan, Israel, 5262000
- Chaim Sheba Medical Center ( Site 0041)
-
-
-
-
-
Milano, Italy, 20141
- Istituto Europeo di Oncologia ( Site 2040)
-
Siena, Italy, 53100
- Policlinico Le Scotte - A.O. Senese ( Site 2039)
-
-
-
-
-
Seoul, Korea, Republic of, 03080
- Seoul National University Hospital ( Site 1992)
-
Seoul, Korea, Republic of, 03722
- Severance Hospital Yonsei University Health System ( Site 1993)
-
-
-
-
-
Oslo, Norway, 0424
- Oslo Universitetssykehus Radiumhospitalet ( Site 0060)
-
-
-
-
Gauteng
-
Johannesburg, Gauteng, South Africa, 2193
- WITS Clinical Research CMJAH Clinical Trial Site ( Site 0101)
-
Pretoria, Gauteng, South Africa, 0002
- Clinical Research Unit - University of Pretoria ( Site 0102)
-
Pretoria, Gauteng, South Africa, 0081
- Wilgers Oncology Centre ( Site 0103)
-
Pretoria, Gauteng, South Africa, 0181
- Little Company of Mary Hospital ( Site 0100)
-
-
Western Cape
-
Cape Town, Western Cape, South Africa, 7570
- Cape Town Oncology Trials Pty Ltd ( Site 0104)
-
-
-
-
Gipuzkoa
-
San Sebastian, Gipuzkoa, Spain, 20014
- Onkologikoa - Instituto Oncologico de San Sebastian ( Site 0088)
-
-
Navarra
-
Pamplona, Navarra, Spain, 31008
- Clinica Universitaria de Navarra. ( Site 0082)
-
-
Valenciana, Comunitat
-
Valencia, Valenciana, Comunitat, Spain, 46010
- Hospital Clinico Universitario de Valencia ( Site 0090)
-
-
-
-
Michigan
-
Detroit, Michigan, United States, 48202
- Henry Ford Hospital ( Site 0008)
-
-
New Jersey
-
New Brunswick, New Jersey, United States, 08903
- Rutgers Cancer Institute of New Jersey ( Site 0002)
-
-
Oregon
-
Portland, Oregon, United States, 97213
- Providence Portland Medical Center [Portland, OR] ( Site 0005)
-
-
Washington
-
Tacoma, Washington, United States, 98405
- Northwest Medical Specialties, PLLC ( Site 0006)
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Has histologically or cytologically confirmed diagnosis of advanced/metastatic melanoma.
- Has Stage III or Stage IV melanoma.
- Must be naive to anti-PD-L1 treatment, talimogene laherparepvec (TVEC) and other oncolytic viruses.
Has 2 lesions as defined below:
- At least 1 cutaneous or subcutaneous lesion that is amenable to IT injection and biopsy and measurable per RECIST 1.1
- At least 1 distant and/or discrete noninjected lesion that is amenable to biopsy and measurable per RECIST 1.1
- Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
- Demonstrates adequate organ function
- Male participants refrain from donating sperm during the intervention period and for at least 120 days after the last dose of study intervention PLUS are either abstinent from heterosexual intercourse OR agree to use approved contraception during that period
- Female participants are not pregnant or breastfeeding and are not a woman of childbearing potential (WOCBP) OR are a WOCBP that agrees to use contraception during the treatment and for at least 120 days after the last dose of study intervention
- Has measurable disease per RECIST 1.1
- Is able to provide newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
Human Immunodeficiency Virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy (ART), defined as:
- Must have Cluster of Differentiation 4 (CD4)+ T-cell count >350 cells/mm^3 at time of screening
- Must have achieved and maintained virologic suppression
- Must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry
- The combination ART regimen must not contain any antiretroviral medication other than abacavir, dolutegravir, emtricitabine, lamivudine, raltegravir, rilpivirine, or tenofovir
Exclusion Criteria:
- Has had chemotherapy, definitive radiation, or biological cancer therapy or an investigational agent or investigational device within 4 weeks prior to the first dose of study intervention or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
- Has ocular melanoma
- Has radiographic evidence of major blood vessel infiltration
- Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
- Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy
- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the study requirements
- Has undergone allogeneic hematopoietic stem cell transplantation within the last 5 years
- Has not fully recovered from major surgery without significant detectable infection
- Active cardiovascular disease (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure or serious cardiac arrhythmia requiring medication
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or other agents such as cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), OX-40, Cluster of Differentiation 137 (CD137)
- Has received a live vaccine within 30 days prior to the first dose of study drug
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy in excess of replacement doses or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
- Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has hypersensitivity to pembrolizumab and/or any of its excipients
- Has hypersensitivity to gebasaxturev or any of its excipients
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Has an active infection requiring systemic therapy
- Has a known history of Hepatitis B or known active Hepatitis C virus infection
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
- Has had an allogenic tissue/solid organ transplant
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: IV Gebasaxturev + Pembrolizumab
Participants receive gebasaxturev at a dose of 1 X 10^9 TCID50 by IV infusion on Days 1, 3, 5, and 8 of Cycle 1 (28-day cycle) and Day 1 of Cycles 2-8 (21-day cycles) plus pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle.
Gebasaxturev will be administered for up to 8 cycles (up to 6 months).
Pembrolizumab will be administered for up to 35 cycles (up to 2 years).
|
Administered as an IV infusion of 1 X 10^9 TCID50
Other Names:
Administered as an IV infusion of 200 mg
Other Names:
|
Experimental: ITu Gebasaxturev + Pembrolizumab
Participants receive gebasaxturev at a dose of 3 X 10^8 TCID50 by ITu injection on Days 1, 3, 5, and 8 of Cycle 1 (28-day cycle) and Day 1 of Cycles 2-8 (21-day cycles) plus pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle.
Gebasaxturev will be administered for up to 8 cycles (up to 6 months).
Pembrolizumab will be administered for up to 35 cycles (up to 2 years).
|
Administered as an IV infusion of 200 mg
Other Names:
Administered as an ITu injection of 3 X 10^8 TCID50
Other Names:
|
Experimental: Pembrolizumab
Participants receive pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle.
Pembrolizumab will be administered for up to 35 cycles (up to 2 years).
|
Administered as an IV infusion of 200 mg
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Time Frame: Up to 3 years
|
ORR is defined as the percentage of participants who have a Complete Response (CR: disappearance of all lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions, without evidence of progression based on non-target or new lesions) as assessed by BICR per RECIST 1.1 which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
The percentage of participants who experience a CR or PR based on modified RECIST 1.1 will be presented.
|
Up to 3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival (PFS) per RECIST 1.1 as Assessed by BICR
Time Frame: Up to 3 years
|
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first.
Per RECIST 1.1, PD is defined as either a 20% increase from nadir in target lesions, unequivocal progression of non-target lesions, or the appearance of new lesions.
PFS will be assessed by BICR for this outcome measure.
|
Up to 3 years
|
Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR
Time Frame: Up to 3 years
|
For participants who demonstrate a confirmed complete response (CR: disappearance of all lesions) or confirmed Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions, without evidence of progression based on non-target or new lesions.)
per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and will be assessed by BICR for this outcome measure.
|
Up to 3 years
|
ORR per RECIST 1.1 as Assessed by the Investigator
Time Frame: Up to 3 years
|
ORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions, without evidence of progression based on non-target or new lesions.)
as assessed by the investigator per RECIST 1.1, which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
The percentage of participants who experience a CR or PR based on modified RECIST 1.1 will be presented.
|
Up to 3 years
|
PFS per RECIST 1.1 as Assessed by the Investigator
Time Frame: Up to 3 years
|
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first.
Per RECIST 1.1, PD is defined as either a 20% increase from nadir in target lesions, unequivocal progression of non-target lesions, or the appearance of new lesions.
PFS will be assessed by the investigator for this outcome measure.
|
Up to 3 years
|
DOR per RECIST 1.1 as Assessed by the Investigator
Time Frame: Up to 3 years
|
For participants who demonstrate a confirmed complete response (CR: disappearance of all lesions) or confirmed Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death.
DOR will be assessed by the investigator for this outcome measure.
|
Up to 3 years
|
Overall Survival (OS)
Time Frame: Up to 3 years
|
OS is defined as the time from the date of study treatment to the date of death due to any cause.
|
Up to 3 years
|
Number of Participants with One or More Adverse Events (AEs)
Time Frame: Up to 30 days after last dose (up to 3 years)
|
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
The percentage of participants who experience at least one AE will be reported.
|
Up to 30 days after last dose (up to 3 years)
|
Number of Participants who Discontinue Study Drug Due to an AE
Time Frame: Up to 2 years
|
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
The percentage of participants who discontinue study treatment due to an AE will be reported.
|
Up to 2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 5, 2020
Primary Completion (Actual)
July 12, 2023
Study Completion (Actual)
July 12, 2023
Study Registration Dates
First Submitted
November 4, 2019
First Submitted That Met QC Criteria
November 4, 2019
First Posted (Actual)
November 5, 2019
Study Record Updates
Last Update Posted (Estimated)
March 4, 2024
Last Update Submitted That Met QC Criteria
March 1, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Pembrolizumab
Other Study ID Numbers
- V937-011
- 2019-002034-36 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced/Metastatic Melanoma
-
MorphotekTerminatedMelanoma | Metastatic Melanoma | Advanced Melanoma | Malignant Metastatic MelanomaUnited States
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingAdvanced Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm | Unresectable MelanomaUnited States
-
Elizabeth DavisBristol-Myers SquibbTerminatedMetastatic Melanoma | Advanced Melanoma | Metastatic Melanoma Stratified by MHC-II ExpressionUnited States
-
Institut Paoli-CalmettesSociété Francophone d'Onco-GériatrieUnknownAdvanced or Metastatic NSCLC | Advanced or Metastatic MelanomaFrance
-
Regeneron PharmaceuticalsBristol-Myers SquibbCompletedMelanoma | Metastatic Melanoma | Unresectable Melanoma | Advanced MelanomaUnited States
-
Regeneron PharmaceuticalsBristol-Myers SquibbActive, not recruitingMelanoma | Metastatic Melanoma | Unresectable Melanoma | Advanced MelanomaUnited States
-
Millennium Pharmaceuticals, Inc.CompletedAdvanced Metastatic Melanoma | Advanced Non-hematologic MalignanciesUnited States
-
Cancer Trials IrelandCompletedMetastatic Melanoma | Advanced MelanomaIreland
-
Bristol-Myers SquibbCompletedMetastatic Melanoma | Advanced MelanomaUnited States, Netherlands, Spain
-
Shanghai Junshi Bioscience Co., Ltd.UnknownMetastatic Melanoma | Advanced MelanomaChina
Clinical Trials on Gebasaxturev IV
-
Taipei City HospitalNot yet recruitingAcute Flank PainTaiwan
-
Healthgen Biotechnology Corp.RecruitingEmphysema Secondary to Congenital AATDUnited States
-
Eli Lilly and CompanyCompletedPsoriasisUnited States
-
Kyowa Kirin Co., Ltd.Terminated
-
Healthgen Biotechnology Corp.Completed
-
Eli Lilly and CompanyCompletedAlzheimer DiseaseUnited States, Japan
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
Asir John SamuelMaharishi Markendeswar University (Deemed to be University)RecruitingAcute Coronary SyndromeIndia
-
WockhardtCompletedBioavailabilityUnited States
-
Prometheus Biosciences, Inc., a subsidiary of Merck...Altasciences Company Inc.Completed