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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04152863




Registration number
NCT04152863
Ethics application status
Date submitted
4/11/2019
Date registered
5/11/2019
Date last updated
6/08/2024

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
V937-011
Secondary ID [2] 0 0
V937-011
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced/Metastatic Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Gebasaxturev IV
Treatment: Other - Gebasaxturev ITu
Treatment: Drugs - Pembrolizumab

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).

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).

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).


Treatment: Other: Gebasaxturev IV
Administered as an IV infusion of 1 X 10\^9 TCID50

Treatment: Other: Gebasaxturev ITu
Administered as an ITu injection of 3 X 10\^8 TCID50

Treatment: Drugs: Pembrolizumab
Administered as an IV infusion of 200 mg
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
Up to ~ 35 months
Secondary outcome [1] 0 0
Progression Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR
Timepoint [1] 0 0
Up to ~ 35 months
Secondary outcome [2] 0 0
Duration of Response (DOR)
Timepoint [2] 0 0
Up to ~ 35 months
Secondary outcome [3] 0 0
Objective Response Rate (ORR) Per RECIST 1.1, as Assessed by the Investigator
Timepoint [3] 0 0
Up to ~ 35 months
Secondary outcome [4] 0 0
Progression Free Survival (PFS) RECIST 1.1, as Assessed by the Investigator
Timepoint [4] 0 0
Up to ~ 35 months
Secondary outcome [5] 0 0
Duration of Response (DOR) Per RECIST 1.1, as Assessed by the Investigator
Timepoint [5] 0 0
Up to ~ 35 months
Secondary outcome [6] 0 0
Overall Survival (OS)
Timepoint [6] 0 0
Up to ~ 35 months
Secondary outcome [7] 0 0
Percentage of Participants Who Experienced an Adverse Event (AE)
Timepoint [7] 0 0
Up to ~ 37 months
Secondary outcome [8] 0 0
Percentage of Participants Who Discontinued Study Drug Due to an AE
Timepoint [8] 0 0
Up to ~ 27 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/07/2023
Sample size
Target
Accrual to date
Final
85
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
The Queen Elizabeth Hospital ( Site 0143) - Woodville
Recruitment hospital [2] 0 0
Alfred Health ( Site 0142) - Melbourne
Recruitment hospital [3] 0 0
Fiona Stanley Hospital ( Site 0141) - Murdoch
Recruitment postcode(s) [1] 0 0
5011 - Woodville
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Michigan
Country [2] 0 0
United States of America
State/province [2] 0 0
New Jersey
Country [3] 0 0
United States of America
State/province [3] 0 0
Oregon
Country [4] 0 0
United States of America
State/province [4] 0 0
Washington
Country [5] 0 0
Chile
State/province [5] 0 0
Region M. De Santiago
Country [6] 0 0
France
State/province [6] 0 0
Cote-d Or
Country [7] 0 0
France
State/province [7] 0 0
Isere
Country [8] 0 0
Germany
State/province [8] 0 0
Baden-Wurttemberg
Country [9] 0 0
Germany
State/province [9] 0 0
Bayern
Country [10] 0 0
Germany
State/province [10] 0 0
Sachsen
Country [11] 0 0
Israel
State/province [11] 0 0
Haifa
Country [12] 0 0
Israel
State/province [12] 0 0
Jerusalem
Country [13] 0 0
Israel
State/province [13] 0 0
Ramat Gan
Country [14] 0 0
Italy
State/province [14] 0 0
Milano
Country [15] 0 0
Italy
State/province [15] 0 0
Siena
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Seoul
Country [17] 0 0
Norway
State/province [17] 0 0
Oslo
Country [18] 0 0
South Africa
State/province [18] 0 0
Gauteng
Country [19] 0 0
South Africa
State/province [19] 0 0
Western Cape
Country [20] 0 0
Spain
State/province [20] 0 0
Gipuzkoa
Country [21] 0 0
Spain
State/province [21] 0 0
Navarra
Country [22] 0 0
Spain
State/province [22] 0 0
Valenciana, Comunitat

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04152863
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04152863