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)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Advanced/Metastatic Melanoma
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)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-11-05
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 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

Primary outcomes:
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)
timeFrame: Up to ~ 35 months
Secondary outcomes:
measure: Progression Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR
timeFrame: Up to ~ 35 months
measure: Duration of Response (DOR)
timeFrame: Up to ~ 35 months
measure: Objective Response Rate (ORR) Per RECIST 1.1, as Assessed by the Investigator
timeFrame: Up to ~ 35 months
measure: Progression Free Survival (PFS) RECIST 1.1, as Assessed by the Investigator
timeFrame: Up to ~ 35 months
measure: Duration of Response (DOR) Per RECIST 1.1, as Assessed by the Investigator
timeFrame: Up to ~ 35 months
measure: Overall Survival (OS)
timeFrame: Up to ~ 35 months
measure: Percentage of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to ~ 37 months
measure: Percentage of Participants Who Discontinued Study Drug Due to an AE
timeFrame: Up to ~ 27 months
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Henry Ford Hospital ( Site 0008)
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey ( Site 0002)
state: New Jersey
city: Portland
country: United States
facility: Providence Portland Medical Center [Portland, OR] ( Site 0005)
state: Oregon
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC ( Site 0006)
state: Washington
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital ( Site 0143)
state: South Australia
city: Melbourne
country: Australia
facility: Alfred Health ( Site 0142)
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital ( Site 0141)
state: Western Australia
city: Santiago
country: Chile
facility: FALP-UIDO ( Site 2062)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Bradfordhill-Clinical Area ( Site 2061)
state: Region M. De Santiago
city: Dijon
country: France
facility: Centre Georges Francois Leclerc ( Site 2025)
state: Cote-d Or
city: La Tronche
country: France
facility: CHU de Grenoble Hopital Nord ( Site 2027)
state: Isere
city: Tübingen
country: Germany
facility: Universitaetsklinikum Tuebingen-Hautklinik ( Site 2001)
state: Baden-Wurttemberg
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg ( Site 2007)
state: Bayern
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig AOeR ( Site 2005)
state: Sachsen
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology Division ( Site 0040)
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical Center ( Site 0042)
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center ( Site 0041)
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia ( Site 2040)
city: Siena
country: Italy
facility: Policlinico Le Scotte - A.O. Senese ( Site 2039)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 1992)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System ( Site 1993)
city: Oslo
country: Norway
facility: Oslo Universitetssykehus Radiumhospitalet ( Site 0060)
city: Johannesburg
country: South Africa
facility: WITS Clinical Research CMJAH Clinical Trial Site ( Site 0101)
state: Gauteng
city: Pretoria
country: South Africa
facility: Clinical Research Unit - University of Pretoria ( Site 0102)
state: Gauteng
city: Pretoria
country: South Africa
facility: Wilgers Oncology Centre ( Site 0103)
state: Gauteng
city: Pretoria
country: South Africa
facility: Little Company of Mary Hospital ( Site 0100)
state: Gauteng
city: Cape Town
country: South Africa
facility: Cape Town Oncology Trials Pty Ltd ( Site 0104)
state: Western Cape
city: San Sebastian
country: Spain
facility: Onkologikoa - Instituto Oncologico de San Sebastian ( Site 0088)
state: Gipuzkoa
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra. ( Site 0082)
state: Navarra
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia ( Site 0090)
state: Valenciana, Comunitat
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.