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)

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: Advanced/Metastatic Melanoma
• Intervention / Treatment: Biological: Gebasaxturev IV; Drug: Pembrolizumab; Biological: Gebasaxturev ITu

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • 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)
• Chile
  • 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)
• France
  • 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)
• Germany
  • 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)
• Israel
  • 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)
• Italy
  • Milano, Italy, 20141
    • Istituto Europeo di Oncologia ( Site 2040)
  • Siena, Italy, 53100
    • Policlinico Le Scotte - A.O. Senese ( Site 2039)
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital ( Site 1992)
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System ( Site 1993)
• Norway
  • Oslo, Norway, 0424
    • Oslo Universitetssykehus Radiumhospitalet ( Site 0060)
• South Africa
  • 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)
• Spain
  • 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)
• United States
  • 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

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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

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).	Biological: Gebasaxturev IV; Administered as an IV infusion of 1 X 10^9 TCID50; Other Names: Coxsackievirus A21 (CVA21); Formerly known as CAVATAK®; CAV21; V937; Drug: Pembrolizumab; Administered as an IV infusion of 200 mg; Other Names: MK-3475; Keytruda®
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).	Drug: Pembrolizumab; Administered as an IV infusion of 200 mg; Other Names: MK-3475; Keytruda®; Biological: Gebasaxturev ITu; Administered as an ITu injection of 3 X 10^8 TCID50; Other Names: Coxsackievirus A21 (CVA21); Formerly known as CAVATAK®; CAV21; V937
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).	Drug: Pembrolizumab; Administered as an IV infusion of 200 mg; Other Names: MK-3475; Keytruda®

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)	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.	Up to ~ 35 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced an Adverse Event (AE)	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.	Up to ~ 37 months
Progression Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR	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.	Up to ~ 35 months
Duration of Response (DOR)	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.	Up to ~ 35 months
Objective Response Rate (ORR) Per RECIST 1.1, as Assessed by the Investigator	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.	Up to ~ 35 months
Progression Free Survival (PFS) RECIST 1.1, as Assessed by the Investigator	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.	Up to ~ 35 months
Duration of Response (DOR) Per RECIST 1.1, as Assessed by the Investigator	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.	Up to ~ 35 months
Overall Survival (OS)	OS is the time from randomization to death due to any cause.	Up to ~ 35 months
Percentage of Participants Who Discontinued Study Drug Due to an AE	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.	Up to ~ 27 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Deng JZ, Rustandi RR, Barbacci D, Swartz AR, Gulasarian A, Loughney JW. Reverse-Phase Ultra-Performance Chromatography Method for Oncolytic Coxsackievirus Viral Protein Separation and Empty to Full Capsid Quantification. Hum Gene Ther. 2022 Jul;33(13-14):765-775. doi: 10.1089/hum.2022.013. Epub 2022 Jun 1.

Helpful Links

• Merck Clinical Trials Information

Study record dates

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 (Actual): August 6, 2024
• Last Update Submitted That Met QC Criteria: July 11, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Coxsackievirus A21; programmed cell death 1 (PD-1, PD1); programmed cell death ligand 1 (PD-L1, PDL1); programmed cell death ligand 2 (PD-L2, PDL2); Intracellular Adhesion Molecule-1 (ICAM-1)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: V937-011 (Other Identifier: Merck Id); 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