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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04152863
Ethics application status
Date submitted
4/11/2019
Date registered
5/11/2019
Date last updated
23/11/2020

Titles & IDs
Public 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)
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
2019-002034-36
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
Other interventions - V937 IV
Other interventions - V937 ITu
Treatment: Drugs - Pembrolizumab

Experimental: IV V937 + Pembrolizumab - Participants 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).

Experimental: ITu V937 + Pembrolizumab - Participants receive V937 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. 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).

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).


Other interventions: V937 IV
Administered as an IV infusion of 1 X 10^9 TCID50

Other interventions: V937 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
Other interventions
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) - 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.
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Progression-free Survival (PFS) per RECIST 1.1 as Assessed by BICR - 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.
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR - 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.
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [3] 0 0
ORR per RECIST 1.1 as Assessed by the Investigator - 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.
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
PFS per 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, 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.
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [5] 0 0
DOR per RECIST 1.1 as Assessed by the Investigator - 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.
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [6] 0 0
Overall Survival (OS) - OS is defined as the time from the date of study treatment to the date of death due to any cause.
Timepoint [6] 0 0
Up to 3 years
Secondary outcome [7] 0 0
Number of Participants with One or More Adverse Events (AEs) - 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.
Timepoint [7] 0 0
Up to 30 days after last dose (up to 3 years)
Secondary outcome [8] 0 0
Number of Participants who Discontinue Study Drug Due to an AE - 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.
Timepoint [8] 0 0
Up to 2 years

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
Gender
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 V937 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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Alfred Health ( Site 0142) - Melbourne
Recruitment hospital [2] 0 0
Fiona Stanley Hospital ( Site 0141) - Murdoch
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment postcode(s) [2] 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
France
State/province [5] 0 0
Bourgogne
Country [6] 0 0
Israel
State/province [6] 0 0
Haifa
Country [7] 0 0
Israel
State/province [7] 0 0
Jerusalem
Country [8] 0 0
Israel
State/province [8] 0 0
Ramat Gan
Country [9] 0 0
Italy
State/province [9] 0 0
Toscana
Country [10] 0 0
Italy
State/province [10] 0 0
Milano
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Seoul
Country [12] 0 0
Norway
State/province [12] 0 0
Oslo
Country [13] 0 0
South Africa
State/province [13] 0 0
Gauteng
Country [14] 0 0
South Africa
State/province [14] 0 0
Western Cape
Country [15] 0 0
Spain
State/province [15] 0 0
Gipuzkoa
Country [16] 0 0
Spain
State/province [16] 0 0
Navarra
Country [17] 0 0
Spain
State/province [17] 0 0
Valenciana, Comunitat

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 2 study to assess the efficacy, safety, and tolerability of V937 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 V937 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.
Trial website
https://clinicaltrials.gov/show/NCT04152863
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

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