The purpose of this study is to evaluate the safety, tolerability, and efficacy in participants with advanced/metastatic or recurrent malignancies who receive gebasaxturev (V937) in combination with pembrolizumab (MK-3475). The primary objective for Part 1 is to evaluate the objective response rate, and the primary objective for Part 2 is to determine the safety and tolerability of gebasaxturev administered in combination with pembrolizumab. With Amendment 4, this study will be terminated once all participants who have completed or discontinued gebasaxturev treatment and are only receiving pembrolizumab may be enrolled in a pembrolizumab extension study, if available, to continue pembrolizumab monotherapy for up to 35 cycles from first pembrolizumab dose on V937-013.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
76
Participants receive gebasaxturev intratumorally for 1 28-day cycle followed by 7 21-day cycles.
Participants receive pembrolizumab intravenously for 1 28-day cycle followed by 34 21-day cycles.
John Theurer Cancer Center ( Site 0004)
Hackensack, New Jersey, United States
Providence Portland Medical Center ( Site 0001)
Portland, Oregon, United States
Princess Margaret Cancer Centre ( Site 0031)
Toronto, Ontario, Canada
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0032)
Montreal, Quebec, Canada
Centre Hospitalier Lyon-Sud ( Site 0055)
Pierre-Bénite, Auvergne-Rhône-Alpes, France
Part 1: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions and no new lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 30 months
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
The following toxicities during DLT evaluation period were considered a DLT, if assessed by investigator to be possibly, probably, or definitely related to treatment: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except Gr 3 thrombocytopenia (if associated with clinically significant bleeding) or any grade febrile neutropenia; nonhematologic adverse event (AE) ≥ Gr 3 (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention is required, leads to hospitalization, or persists for \>1 week); drug-related toxicity that causes a \>2 week delay in Cycle 2 initiation; drug-related toxicity that causes treatment discontinuation or missed dosage of gebasaxturev; or Gr 5 toxicity. Per protocol, only the participants in Part 2 were analyzed in this outcome measure.
Time frame: Cycle 1 (28-day cycle)
Part 2: Number of Participants Who Experienced One or More Adverse Events (AEs)
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 2 were analyzed in this outcome measure.
Time frame: Up to approximately 29 months
Part 2: Number of Participants Who Discontinued Study Intervention Due to an AE
An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 2 were analyzed in this outcome measure.
Time frame: Up to approximately 10 months
Part 1: Number of Participants Who Experienced One or More AEs
An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 30 months
Part 1: Number of Participants Who Discontinued Study Intervention Due to an AE
An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 23 months
Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator
PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by investigator. Per RECIST 1.1, PD is 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. The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 30 months
Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator
For participants who demonstrated a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death, whichever occurs first. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection did not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
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Hopital La Timone ( Site 0051)
Marseille, Bouches-du-Rhone, France
Gustave Roussy ( Site 0053)
Villejuif, Val-de-Marne, France
Universitaetsklinikum Heidelberg-Nationales Centrum für Tumorerkrankungen ( Site 0172)
Heidelberg, Baden-Wurttemberg, Germany
Universitaetsklinikum Tuebingen ( Site 0171)
Tübingen, Baden-Wurttemberg, Germany
Orszagos Onkologiai Intezet ( Site 0070)
Budapest, Hungary
...and 19 more locations
Time frame: Up to approximately 30 months
PFS Per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator
PFS was defined as the time from first dose of study treatment to the first documented immune-based confirmed progressive disease (iCPD) or death due to any cause, whichever occurs first as assessed by investigator. Per iRECIST, iCPD was defined as worsening of any existing cause of progression, or the appearance of any other cause of progression, relative to the initial appearance of progressive disease by RECIST 1.1. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 30 months
DOR Per iRECIST as Assessed by Investigator
For participants who demonstrated confirmed CR (disappearance of all target lesions and non-target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 or immune-based Complete Response (iCR: Disappearance of all target lesions) or immune-based Partial Response (iPR: ≥30% decrease in the sum of diameters of target lesions) after a single PD per iRECIST, DOR was defined as the time from the first documented CR or PR, or iCR or an iPR, as assessed by investigator, until progressive disease or death, whichever occurs first. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection did not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 30 months
ORR Per iRECIST as Assessed by Investigator
ORR was defined as the percentage of participants who had confirmed responses assessed using RECIST 1.1 before PD or an immune-based Complete Response (iCR: Disappearance of all target lesions) or an immune-based Partial Response (iPR: ≥30% decrease in the sum of diameters of target lesions) after a single PD per iRECIST as assessed by investigator.
Time frame: Up to approximately 30 months
Overall Survival (OS)
OS was defined as the time from first dose of study intervention to death due to any cause. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 30 months
Part 2: ORR Per RECIST 1.1 as Assessed by Investigator
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions and no new lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. Per protocol, only participants in Part 2 were analyzed for this outcome measure.
Time frame: Up to approximately 29 months