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)

NCT ID: NCT04152863

Last Updated: 2024-08-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-05
• Study Completion Date: 2023-07-12

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.

Conditions

Advanced/Metastatic Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Gebasaxturev IV

Intervention Type: BIOLOGICAL

Administered as an IV infusion of 1 X 10\^9 TCID50

Pembrolizumab

Intervention Type: DRUG

Administered as an IV infusion of 200 mg

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).

Group Type: EXPERIMENTAL

Gebasaxturev ITu

Intervention Type: BIOLOGICAL

Administered as an ITu injection of 3 X 10\^8 TCID50

Pembrolizumab

Intervention Type: DRUG

Administered as an IV infusion of 200 mg

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).

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

Administered as an IV infusion of 200 mg

Interventions

Gebasaxturev IV

Administered as an IV infusion of 1 X 10\^9 TCID50

Intervention Type: BIOLOGICAL

Gebasaxturev ITu

Administered as an ITu injection of 3 X 10\^8 TCID50

Intervention Type: BIOLOGICAL

Pembrolizumab

Administered as an IV infusion of 200 mg

Intervention Type: DRUG

Other Intervention Names

Coxsackievirus A21 (CVA21); Formerly known as CAVATAK®; CAV21; V937; Coxsackievirus A21 (CVA21); Formerly known as CAVATAK®; CAV21; V937; MK-3475; Keytruda®

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Henry Ford Hospital ( Site 0008)

Detroit, Michigan, United States

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

Northwest Medical Specialties, PLLC ( Site 0006)

Tacoma, Washington, United States

The Queen Elizabeth Hospital ( Site 0143)

Woodville, South Australia, Australia

Alfred Health ( Site 0142)

Melbourne, Victoria, Australia

Fiona Stanley Hospital ( Site 0141)

Murdoch, Western Australia, Australia

FALP-UIDO ( Site 2062)

Santiago, Region M. de Santiago, Chile

Bradfordhill-Clinical Area ( Site 2061)

Santiago, Region M. de Santiago, Chile

Centre Georges Francois Leclerc ( Site 2025)

Dijon, Cote-d Or, France

CHU de Grenoble Hopital Nord ( Site 2027)

La Tronche, Isere, France

Universitaetsklinikum Tuebingen-Hautklinik ( Site 2001)

Tübingen, Baden-Wurttemberg, Germany

Universitaetsklinikum Regensburg ( Site 2007)

Regensburg, Bavaria, Germany

Universitaetsklinikum Leipzig AOeR ( Site 2005)

Leipzig, Saxony, Germany

Rambam Health Care Campus-Oncology Division ( Site 0040)

Haifa, , Israel

Hadassah Ein Kerem Medical Center ( Site 0042)

Jerusalem, , Israel

Chaim Sheba Medical Center ( Site 0041)

Ramat Gan, , Israel

Istituto Europeo di Oncologia ( Site 2040)

Milan, , Italy

Policlinico Le Scotte - A.O. Senese ( Site 2039)

Siena, , Italy

Oslo Universitetssykehus Radiumhospitalet ( Site 0060)

Oslo, , Norway

WITS Clinical Research CMJAH Clinical Trial Site ( Site 0101)

Johannesburg, Gauteng, South Africa

Clinical Research Unit - University of Pretoria ( Site 0102)

Pretoria, Gauteng, South Africa

Wilgers Oncology Centre ( Site 0103)

Pretoria, Gauteng, South Africa

Little Company of Mary Hospital ( Site 0100)

Pretoria, Gauteng, South Africa

Cape Town Oncology Trials Pty Ltd ( Site 0104)

Cape Town, Western Cape, South Africa

Seoul National University Hospital ( Site 1992)

Seoul, , South Korea

Severance Hospital Yonsei University Health System ( Site 1993)

Seoul, , South Korea

Onkologikoa - Instituto Oncologico de San Sebastian ( Site 0088)

Donostia / San Sebastian, Gipuzkoa, Spain

Clinica Universitaria de Navarra. ( Site 0082)

Pamplona, Navarre, Spain

Hospital Clinico Universitario de Valencia ( Site 0090)

Valencia, Valenciana, Comunitat, Spain

Countries

United States; Australia; Chile; France; Germany; Israel; Italy; Norway; South Africa; South Korea; Spain

References

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.

Reference Type: DERIVED

PMID: 35387488 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

Other Identifiers

V937-011

Identifier Type: OTHER

Identifier Source: secondary_id

2019-002034-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

V937-011

Identifier Type: -

Identifier Source: org_study_id