Clinical Trials /

Efficacy, Safety, and Tolerability of V937 Administered Intravenously or Intratumorally With Pembrolizumab (MK-3475) Versus Pembrolizumab Alone in Participants With Advanced/Metastatic Melanoma (V937-011)

NCT04152863

Description:

This is a Phase 2 study to assess the efficacy, safety, and tolerability of V937 administered both intratumorally (IT) 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 V937 administered either IT 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.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy, Safety, and Tolerability of V937 Administered Intravenously or Intratumorally With Pembrolizumab (MK-3475) Versus Pembrolizumab Alone in Participants With Advanced/Metastatic Melanoma (V937-011)
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: V937-011
  • SECONDARY ID: 2019-002034-36
  • NCT ID: NCT04152863

Conditions

  • Advanced/Metastatic Melanoma

Interventions

DrugSynonymsArms
V937 IVCoxsackievirus A21 (CVA21), Formerly known as CAVATAK®, CAV21IT V937 + Pembrolizumab
V937 ITCoxsackievirus A21 (CVA21), Formerly known as CAVATAK®, CAV21IT V937 + Pembrolizumab
PembrolizumabMK-3475, Keytruda®IT V937 + Pembrolizumab

Purpose

This is a Phase 2 study to assess the efficacy, safety, and tolerability of V937 administered both intratumorally (IT) 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 V937 administered either IT 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.

Trial Arms

NameTypeDescriptionInterventions
IV V937 + PembrolizumabExperimentalParticipants receive V937 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. V937 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).
  • V937 IV
  • V937 IT
  • Pembrolizumab
IT V937 + PembrolizumabExperimentalParticipants receive V937 at a dose of 3 X 10^8 TCID50 by IT 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. V937 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).
  • V937 IV
  • V937 IT
  • Pembrolizumab
PembrolizumabExperimentalParticipants 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).
  • Pembrolizumab

Eligibility Criteria

        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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Progression-free Survival (PFS) per RECIST 1.1 as Assessed by BICR
Time Frame:Up to 3 years
Safety Issue:
Description: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.
Measure:Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR
Time Frame:Up to 3 years
Safety Issue:
Description: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.
Measure:ORR per RECIST 1.1 as Assessed by the Investigator
Time Frame:Up to 3 years
Safety Issue:
Description: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.
Measure:ORR per RECIST 1.1 for Immune-based Therapeutics (iRECIST) as Assessed by the Investigator
Time Frame:Up to 3 years
Safety Issue:
Description:ORR is defined as an immune-based Complete Response (iCR: disappearance of all lesions) or immune-based Partial Response (iPR: at least a 30% decrease in the sum of diameters of target lesions) as assessed by the investigator. The percentage of participants who experience an iCR or iPR will be presented.
Measure:PFS per RECIST 1.1 as Assessed by the Investigator
Time Frame:Up to 3 years
Safety Issue:
Description: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.
Measure:PFS per iRECIST as Assessed by the Investigator
Time Frame:Up to 3 years
Safety Issue:
Description:PFS is defined as the time from randomization to the first documented immune-based confirmed progressive disease (iCPD) or death due to any cause, whichever occurs first. Per iRECIST, iCPD is defined as worsening of any existing cause of progression, or the appearance of any other cause of progression, relative to the initial appearance of progressive disease by RECIST 1.1. PFS will be assessed by the investigator for this outcome measure.
Measure:DOR per RECIST 1.1 as Assessed by the Investigator
Time Frame:Up to 3 years
Safety Issue:
Description: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.
Measure:DOR per iRECIST as Assessed by the Investigator
Time Frame:Up to 3 years
Safety Issue:
Description:For participants who demonstrate a confirmed immune-based complete response (iCR) or a confirmed immune-based Partial Response (iPR) as assessed by the investigator per iRECIST, DOR is defined as the time from first documented evidence of iCR or iPR until disease progression or death. DOR will be assessed by the investigator for this outcome measure.
Measure:Overall Survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:OS is defined as the time from the date of study treatment to the date of death due to any cause.
Measure:Number of Participants with One or More Adverse Events (AEs)
Time Frame:Up to 30 days after last dose (up to 3 years)
Safety Issue:
Description: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.
Measure:Number of Participants who Discontinue Study Drug Due to an AE
Time Frame:Up to 2 years
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • programmed cell death 1 (PD-1, PD1)
  • programmed cell death ligand 1 (PD-L1, PDL1)
  • programmed cell death ligand 2 (PD-L2, PDL2)
  • Coxsackievirus A21
  • Intracellular Adhesion Molecule-1 (ICAM-1)

Last Updated

February 14, 2020