A Study of Gebasaxturev (V937) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors (V937-013)

Neoplasm Metastasis Clinical Trial

Official title:

A Phase 1b/2 Clinical Study of Intratumoral Administration of V937 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04521621
• Other study ID #: V937-013
• Secondary ID: V937-013jRCT2033
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: October 28, 2020
• Est. completion date: July 25, 2023

Study information

• Verified date: March 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 75
• Est. completion date: July 25, 2023
• Est. primary completion date: July 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Locally-advanced disease that is not amenable to surgery or radiation, or Stage IV advanced/metastatic solid tumor malignancies

• Histologically- or cytologically-confirmed diagnosis of an advanced/metastatic solid tumor.

• Measurable disease by RECIST 1.1 criteria as assessed by investigator. Target lesions in a previously irradiated area will be considered measurable if progression has been demonstrated in such lesions

• Submitted a baseline tumor sample for analysis. Participants enrolling in Part 2 Cohorts D-F may enroll without submitting a tumor sample if all other enrollment criteria are met.

• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale obtained within 72 hours prior to the first dose of study intervention

• If participant has known human immunodeficiency virus (HIV)-positive disease, participant must have well-controlled HIV on antiretroviral therapy (ART), per study criteria.

• Adequate organ function

• Male participants are eligible to participate if they agree to the following during the intervention period and for at least 120 days: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR must agree to use contraception unless confirmed to be azoospermic.

• Female participants are eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:

• Is not a woman of childbearing potential (WOCBP)

• Is a WOCBP and using a contraceptive method that is highly effective, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days after the last dose of study intervention.

• Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

• Part 1, All Cohorts: participants must have at least one injectable lesion amenable to injection and/or biopsy.

• Part 1, Cohort A:

• Locally recurrent, inoperable OR metastatic breast cancer treated with at least 1 prior line of therapy in the metastatic setting with skin involvement and/or subcutaneous lesions or accessible lymph nodes amenable to local injection. An exception would be allowed for participants who are not eligible to receive chemotherapy.

• Diagnosis of triple-negative breast cancer (estrogen receptor, progesterone receptor, and HER2-receptor negative status)

• Part 1, Cohort B:

• Histologically confirmed advanced or metastatic head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, hypopharynx, and/or larynx considered incurable and/or treated with no more than 1 previous line of therapy

• Tumors must be PD-L1+

• Documentation of HPV status for oropharyngeal cancers. Other HNSCC subtypes may submit HPV testing, but is not required.

• Part 1, Cohort C:

• Histologically confirmed cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy

• Recurrent/metastatic disease only: Has metastatic disease defined as disseminated disease distant from the initial/primary site of diagnosis and/or with a history of locally-recurrent disease previously treated with surgery and/or radiotherapy, which is now incurable

• Locally-advanced disease only: Must be ineligible for surgical resection per study criteria, and must have received prior radiation therapy to the index site or deemed ineligible for radiation therapy

• Part 2, Solid Tumors+Liver Metastases Dose Level 1-3 arms:

• Histologically-confirmed advanced/metastatic solid tumor that has progressed on all treatment known to confer clinical benefit

• Metastatic liver lesion(s) not exceeding one-third of the total liver volume AND a minimum of one injectable liver lesion

• Part 2, Cohort D:

• Advanced hepatocellular carcinoma (HCC) following progression on, or intolerance to, sorafenib or lenvatinib with no curative options

• Diagnosis of HCC confirmed by radiology, histology, or cytology

• Child-Pugh Class A score

• If a participant has a history of hepatitis C virus (HCV) infection, then the participant must have been successfully treated for this condition

• Controlled (treated) hepatitis B participants will be allowed if they meet protocol-specified criteria

• Participants who are anti-hepatitis B core (HBc) positive, negative for hepatitis B surface antigen (HBsAg), negative or positive for anti-hepatitis B surface (HBs), and who have an HBV viral load under 100 IU/mL, do not require HBV anti-viral prophylaxis

• Part 2, Cohort E:

• Histologically- or cytologically-confirmed diagnosis of locally advanced, unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma

• Received at least one prior line of therapy that includes a platinum/fluoropyrimidine doublet or triplet regimen

• Had proven clinical progression 6 months following (or during) last dose of adjuvant or neo-adjuvant therapy

• Human epidermal growth factor receptor 2 (HER2) negative status; or, those with HER2 positive status AND documented disease progression on a prior regimen containing trastuzumab

Exclusion Criteria:

• Chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to first dose of study intervention, or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better

• If major or minor surgery was performed at/near the area being considered for injection, participant must be recovered from toxicity and/or complications of intervention

• If participant has had injection or radiation therapy, participant must be recovered from toxicity and/or complications of intervention

• History of second malignancy, unless potentially curative treatment has been completed with no further evidence of disease for =5 years.

• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with treated brain metastases may participate if lesions are radiologically stable.

• Active infection requiring therapy, except HIV criteria as stated above, and HBV and HCV criteria for HCC cohort as stated above

• History of interstitial lung disease

• History of noninfectious pneumonitis requiring active steroid therapy or ongoing pneumonitis

• Active autoimmune disease that required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy

• Known Hepatitis B or C infections or known to be positive for HBsAg/HBV deoxyribonucleic acid (DNA) or Hepatitis C Antibody or ribonucleic acid (RNA)

• History of Kaposi's sarcoma and/or Multicentric Castleman's Disease

• Known hypersensitivity to gebasaxturev and/or pembrolizumab or any of their excipients

• Received prior therapy with anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1) agents, Talimogene Laherparepvec (T-VEC), or any other oncolytic virus therapies

• Received a live or live-attenuated vaccine within 30 days prior to first dose of study intervention. Administration of killed vaccines is allowed.

• Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention

• Part 2, Cohort D:

• Has had esophageal or gastric variceal bleeding within the last 6 months

• Has had clinically diagnosed hepatic encephalopathy in the 6 months prior to initiation of study intervention

• Part 2, Cohort E:

• Squamous cell or undifferentiated gastric cancer

Related Conditions & MeSH terms

• Neoplasm Metastasis

Intervention

Biological:
• Gebasaxturev
Participants receive gebasaxturev intratumorally for 1 28-day cycle followed by 7 21-day cycles.

Drug:
• Pembrolizumab
Participants receive pembrolizumab intravenously for 1 28-day cycle followed by 34 21-day cycles.

Locations

Country	Name	City	State
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0032)	Montreal	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0031)	Toronto	Ontario
France	Hopital La Timone ( Site 0051)	Marseille	Bouches-du-Rhone
France	Centre Hospitalier Lyon-Sud ( Site 0055)	Pierre Benite	Rhone-Alpes
France	Gustave Roussy ( Site 0053)	Villejuif	Val-de-Marne
Germany	Universitaetsklinikum Heidelberg-Nationales Centrum für Tumorerkrankungen ( Site 0172)	Heidelberg	Baden-Wurttemberg
Germany	Universitaetsklinikum Tuebingen ( Site 0171)	Tuebingen	Baden-Wurttemberg
Hungary	Orszagos Onkologiai Intezet ( Site 0070)	Budapest
Israel	HaEmek Medical Center ( Site 0071)	Afula
Israel	Hadassah Medical Center. Ein Kerem ( Site 0072)	Jerusalem
Israel	Sourasky Medical Center ( Site 0073)	Tel Aviv
Italy	Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative (	Milano
Japan	National Cancer Center Hospital East ( Site 0166)	Kashiwa	Chiba
Norway	Helse Bergen HF - Haukeland Universitetssykehus ( Site 0162)	Bergen	Hordaland
Norway	Oslo Universitetssykehus Radiumhospitalet ( Site 0161)	Oslo
Peru	Clinica San Gabriel ( Site 0097)	Lima
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 0181	Warszawa	Mazowieckie
Portugal	Centro Hospitalar Universitário Lisboa Norte, E.P.E. - Hospital de Santa Maria ( Site 0192)	Lisbon	Lisboa
Portugal	Instituto Português de Oncologia do Porto Francisco Gentil, EPE ( Site 0191)	Porto
Spain	Hospital Universitari Vall d Hebron ( Site 0121)	Barcelona
Spain	Clinica Universitaria de Navarra ( Site 0122)	Madrid
Taiwan	Chang Gung Medical Foundation - Kaohsiung ( Site 0145)	Kaohsiung
Taiwan	China Medical University Hospital ( Site 0144)	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 0142)	Tainan
Taiwan	Mackay Memorial Hospital ( Site 0143)	Taipei
Taiwan	National Taiwan University Hospital ( Site 0141)	Taipei
Taiwan	Chang Gung Memorial Hospital - Linkou Branch ( Site 0146)	Taoyuan
United States	John Theurer Cancer Center ( Site 0004)	Hackensack	New Jersey
United States	Providence Portland Medical Center ( Site 0001)	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Norway,  Peru,  Poland,  Portugal,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator	ORR is 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. Only the Part 1 arms will be analyzed in this outcome measure.	Up to approximately 44 months
Primary	Number of Participants who Experience a Dose-Limiting Toxicity (DLT)	DLTs are defined as toxicities that: are possibly, probably, or definitely related to study intervention administration; and meet pre-defined study criteria.	Up to approximately 4 weeks
Primary	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. Only the Part 2 arms will be analyzed in this outcome measure.	Up to approximately 107 weeks
Primary	Part 2: Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)	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. Only the Part 2 arms will be analyzed in this outcome measure.	Up to approximately 103 weeks
Secondary	Part 1: 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. Only the Part 1 arms will be analyzed in this outcome measure.	Up to approximately 107 weeks
Secondary	Part 1: Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)	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. Only the Part 1 arms will be analyzed in this outcome measure.	Up to approximately 103 weeks
Secondary	Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator	PFS is 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. Only the Part 1 arms will be analyzed in this outcome measure.	Up to approximately 44 months
Secondary	Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator	For participants who demonstrate a confirmed immune-based 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 is defined as the time from first documented evidence of CR or PR until disease progression or death. 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. Only the Part 1 arms will be analyzed in this outcome measure.	Up to approximately 44 months
Secondary	Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator	PFS is 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 is 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. Only the Part 1 arms will be analyzed in this outcome measure.	Up to approximately 44 months
Secondary	Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator	For participants who demonstrate a confirmed 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) per iRECIST 1.1 as assessed by investigator, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. 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. Only the Part 1 arms will be analyzed in this outcome measure.	Up to approximately 44 months
Secondary	Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator	ORR is defined as the percentage of participants in the analysis population who had 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) per iRECIST 1.1 as assessed by investigator.	Up to approximately 44 months
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 44 months
Secondary	Solid Tumors + Liver Metastases Arms: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator	ORR is 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. Only the Solid Tumors+Liver Metastases Dose Level 1-3 arms will be analyzed in this outcome measure.	Up to approximately 44 months

External Links

•   Merck Clinical Trials Information