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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
85
Administered as an IV infusion of 1 X 10\^9 TCID50
Administered as an ITu injection of 3 X 10\^8 TCID50
Administered as an IV infusion of 200 mg
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
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.
Time frame: Up to ~ 35 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to ~ 35 months
Overall Survival (OS)
OS is the time from randomization to death due to any cause.
Time frame: Up to ~ 35 months
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.
Time frame: Up to ~ 37 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.
Time frame: Up to ~ 27 months
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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
...and 20 more locations