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)
- Conditions
- Advanced/Metastatic Melanoma
- Interventions
- Registration Number
- NCT04152863
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 85
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Has histologically or cytologically confirmed diagnosis of advanced/metastatic melanoma.
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Has Stage III or Stage IV melanoma.
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Must be naive to anti-PD-L1 treatment, talimogene laherparepvec (TVEC) and other oncolytic viruses.
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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
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Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
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Demonstrates adequate organ function
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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
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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
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Has measurable disease per RECIST 1.1
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Is able to provide newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
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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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IV Gebasaxturev + Pembrolizumab Gebasaxturev IV 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). ITu Gebasaxturev + Pembrolizumab Gebasaxturev ITu 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). IV Gebasaxturev + Pembrolizumab 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). Pembrolizumab 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). ITu Gebasaxturev + Pembrolizumab 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).
- Primary Outcome Measures
Name Time Method 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) Up to ~ 35 months ORR was defined as the percentage of participants who experienced 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 was 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 experienced a CR or PR based on modified RECIST 1.1 is presented.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Up to ~ 35 months OS is the time from randomization to death due to any cause.
Progression Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR Up to ~ 35 months PFS was 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 was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD.
Duration of Response (DOR) Up to ~ 35 months For participants who demonstrated 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 was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurred first. RECIST 1.1 was adjusted for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ and was assessed by BICR for this outcome measure.
Objective Response Rate (ORR) Per RECIST 1.1, as Assessed by the Investigator Up to ~ 35 months ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by the investigator modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a CR or PR based on modified RECIST 1.1 was presented.
Progression Free Survival (PFS) RECIST 1.1, as Assessed by the Investigator Up to ~ 35 months 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 as assessed by the investigator, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD.
Duration of Response (DOR) Per RECIST 1.1, as Assessed by the Investigator Up to ~ 35 months For participants who demonstrated 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 as assessed by the investigator, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death.
Percentage of Participants Who Experienced an Adverse Event (AE) Up to ~ 37 months An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Percentage of Participants Who Discontinued Study Drug Due to an AE Up to ~ 27 months An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Trial Locations
- Locations (30)
Universitaetsklinikum Regensburg ( Site 2007)
🇩🇪Regensburg, Bayern, Germany
Rutgers Cancer Institute of New Jersey ( Site 0002)
🇺🇸New Brunswick, New Jersey, United States
Providence Portland Medical Center [Portland, OR] ( Site 0005)
🇺🇸Portland, Oregon, United States
FALP-UIDO ( Site 2062)
🇨🇱Santiago, Region M. De Santiago, Chile
CHU de Grenoble Hopital Nord ( Site 2027)
🇫🇷La Tronche, Isere, France
Rambam Health Care Campus-Oncology Division ( Site 0040)
🇮🇱Haifa, Israel
Universitaetsklinikum Tuebingen-Hautklinik ( Site 2001)
🇩🇪Tübingen, Baden-Wurttemberg, Germany
Universitaetsklinikum Leipzig AOeR ( Site 2005)
🇩🇪Leipzig, Sachsen, Germany
Policlinico Le Scotte - A.O. Senese ( Site 2039)
🇮🇹Siena, Italy
Seoul National University Hospital ( Site 1992)
🇰🇷Seoul, Korea, Republic of
Chaim Sheba Medical Center ( Site 0041)
🇮🇱Ramat Gan, Israel
Severance Hospital Yonsei University Health System ( Site 1993)
🇰🇷Seoul, Korea, Republic of
Istituto Europeo di Oncologia ( Site 2040)
🇮🇹Milano, Italy
Oslo Universitetssykehus Radiumhospitalet ( Site 0060)
🇳🇴Oslo, Norway
WITS Clinical Research CMJAH Clinical Trial Site ( Site 0101)
🇿🇦Johannesburg, Gauteng, South Africa
Wilgers Oncology Centre ( Site 0103)
🇿🇦Pretoria, Gauteng, South Africa
Little Company of Mary Hospital ( Site 0100)
🇿🇦Pretoria, Gauteng, South Africa
Onkologikoa - Instituto Oncologico de San Sebastian ( Site 0088)
🇪🇸San Sebastian, Gipuzkoa, Spain
Hospital Clinico Universitario de Valencia ( Site 0090)
🇪🇸Valencia, Valenciana, Comunitat, Spain
Clinica Universitaria de Navarra. ( Site 0082)
🇪🇸Pamplona, Navarra, Spain
Hadassah Ein Kerem Medical Center ( Site 0042)
🇮🇱Jerusalem, Israel
The Queen Elizabeth Hospital ( Site 0143)
🇦🇺Woodville, South Australia, Australia
Fiona Stanley Hospital ( Site 0141)
🇦🇺Murdoch, Western Australia, Australia
Clinical Research Unit - University of Pretoria ( Site 0102)
🇿🇦Pretoria, Gauteng, South Africa
Alfred Health ( Site 0142)
🇦🇺Melbourne, Victoria, Australia
Northwest Medical Specialties, PLLC ( Site 0006)
🇺🇸Tacoma, Washington, United States
Centre Georges Francois Leclerc ( Site 2025)
🇫🇷Dijon, Cote-d Or, France
Bradfordhill-Clinical Area ( Site 2061)
🇨🇱Santiago, Region M. De Santiago, Chile
Cape Town Oncology Trials Pty Ltd ( Site 0104)
🇿🇦Cape Town, Western Cape, South Africa
Henry Ford Hospital ( Site 0008)
🇺🇸Detroit, Michigan, United States