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

NCT04521621 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: V937-013jRCT20332001912020-001908-42
• Study Type: interventional
• Target: 76
• Locations: 14 countries
• Sites: 29

Brief 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.

Conditions

Neoplasm Metastasis

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Up to approximately 10 months

Secondary Outcomes (9)

• Part 1: Number of Participants Who Experienced One or More AEs

  Up to approximately 30 months

• Part 1: Number of Participants Who Discontinued Study Intervention Due to an AE

  Up to approximately 23 months

• Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator

  Up to approximately 30 months

• Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator

  Up to approximately 30 months

• PFS Per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator

  Up to approximately 30 months

Study Arms (8)

Part 1, Cohort A: Triple-Negative Breast Cancer

EXPERIMENTAL

This arm will enroll participants with triple-negative breast cancer (TNBC) solid tumors. Participants receive 3 X 10\^8 50% tissue culture infectious dose (TCID50) of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days.

Biological: Gebasaxturev; Drug: Pembrolizumab

Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma

EXPERIMENTAL

This arm will enroll participants with head and neck squamous cell carcinoma (HNSCC) solid tumors. Participants receive 3 X 10\^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days.

Biological: Gebasaxturev; Drug: Pembrolizumab

Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma

EXPERIMENTAL

This arm will enroll participants with cutaneous squamous cell carcinoma (cSCC) solid tumors. Participants receive 3 X 10\^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days.

Biological: Gebasaxturev; Drug: Pembrolizumab

Part 2 Dose Level 1, Solid Tumors + Liver Metastases

EXPERIMENTAL

This arm will enroll participants with solid tumors with liver metastases. Participants receive 3 X 10\^7 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days.

Biological: Gebasaxturev; Drug: Pembrolizumab

Part 2 Dose Level 2, Solid Tumors + Liver Metastases

EXPERIMENTAL

This arm will enroll participants with solid tumors with liver metastases. Participants receive 1 X 10\^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days.

Biological: Gebasaxturev; Drug: Pembrolizumab

Part 2 Dose Level 3, Solid Tumors + Liver Metastases

EXPERIMENTAL

This arm will enroll participants with solid tumors with liver metastases. Participants receive 3 X 10\^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days.

Biological: Gebasaxturev; Drug: Pembrolizumab

Part 2, Cohort D: Hepatocellular Carcinoma (HCC)

EXPERIMENTAL

This arm will enroll participants with hepatocellular carcinoma (HCC) solid tumors. Participants receive the gebasaxturev recommended phase 2 dose (RP2D) intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days.

Biological: Gebasaxturev; Drug: Pembrolizumab

Part 2, Cohort E: Gastric Carcinoma

EXPERIMENTAL

This arm will enroll participants with gastric carcinoma solid tumors. Participants receive the gebasaxturev recommended phase 2 dose (RP2D) intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days.

Biological: Gebasaxturev; Drug: Pembrolizumab

Interventions

Gebasaxturev BIOLOGICAL

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

Also known as: Coxsackievirus A21 (CVA21), Formerly known as CAVATAK®, CAV21, V937

Part 1, Cohort A: Triple-Negative Breast Cancer; Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma; Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma; Part 2 Dose Level 1, Solid Tumors + Liver Metastases; Part 2 Dose Level 2, Solid Tumors + Liver Metastases; Part 2 Dose Level 3, Solid Tumors + Liver Metastases; Part 2, Cohort D: Hepatocellular Carcinoma (HCC); Part 2, Cohort E: Gastric Carcinoma

Pembrolizumab DRUG

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

Also known as: MK-3475, KEYTRUDA®

Part 1, Cohort A: Triple-Negative Breast Cancer; Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma; Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma; Part 2 Dose Level 1, Solid Tumors + Liver Metastases; Part 2 Dose Level 2, Solid Tumors + Liver Metastases; Part 2 Dose Level 3, Solid Tumors + Liver Metastases; Part 2, Cohort D: Hepatocellular Carcinoma (HCC); Part 2, Cohort E: Gastric Carcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (29)

John Theurer Cancer Center ( Site 0004)

Hackensack, New Jersey, 07601, United States

Location

Providence Portland Medical Center ( Site 0001)

Portland, Oregon, 97213, United States

Location

Princess Margaret Cancer Centre ( Site 0031)

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0032)

Montreal, Quebec, H2X 3E4, Canada

Location

Centre Hospitalier Lyon-Sud ( Site 0055)

Pierre-Bénite, Auvergne-Rhône-Alpes, 69495, France

Location

Hopital La Timone ( Site 0051)

Marseille, Bouches-du-Rhone, 13005, France

Location

Gustave Roussy ( Site 0053)

Villejuif, Val-de-Marne, 94800, France

Location

Universitaetsklinikum Heidelberg-Nationales Centrum für Tumorerkrankungen ( Site 0172)

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitaetsklinikum Tuebingen ( Site 0171)

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Orszagos Onkologiai Intezet ( Site 0070)

Budapest, 1122, Hungary

Location

HaEmek Medical Center ( Site 0071)

Afula, 1834111, Israel

Location

Hadassah Medical Center. Ein Kerem ( Site 0072)

Jerusalem, 9112001, Israel

Location

Sourasky Medical Center ( Site 0073)

Tel Aviv, 6423906, Israel

Location

Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative (

Milan, 20141, Italy

Location

National Cancer Center Hospital East ( Site 0166)

Kashiwa, Chiba, 277-8577, Japan

Location

Helse Bergen HF - Haukeland Universitetssykehus ( Site 0162)

Bergen, Hordaland, 5021, Norway

Location

Oslo Universitetssykehus Radiumhospitalet ( Site 0161)

Oslo, 0379, Norway

Location

Clinica San Gabriel ( Site 0097)

Lima, 15087, Peru

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 0181

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Centro Hospitalar Universitário Lisboa Norte, E.P.E. - Hospital de Santa Maria ( Site 0192)

Lisbon, Lisbon District, 1649-035, Portugal

Location

Instituto Português de Oncologia do Porto Francisco Gentil, EPE ( Site 0191)

Porto, 4200-072, Portugal

Location

Hospital Universitari Vall d Hebron ( Site 0121)

Barcelona, 08035, Spain

Location

Clinica Universitaria de Navarra ( Site 0122)

Madrid, 28027, Spain

Location

Chang Gung Medical Foundation - Kaohsiung ( Site 0145)

Kaohsiung City, 833, Taiwan

Location

China Medical University Hospital ( Site 0144)

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital ( Site 0142)

Tainan, 704, Taiwan

Location

National Taiwan University Hospital ( Site 0141)

Taipei, 10002, Taiwan

Location

Mackay Memorial Hospital ( Site 0143)

Taipei, 10449, Taiwan

Location

Chang Gung Memorial Hospital - Linkou Branch ( Site 0146)

Taoyuan District, 333, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 35387488 DERIVED

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Neoplasm Metastasis; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2020
• First Posted: August 20, 2020
• Study Start: October 28, 2020
• Primary Completion: July 25, 2023
• Study Completion: July 25, 2023
• Last Updated: October 1, 2024
• Results First Posted: August 7, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share

Locations

DE (2); PL (1); ES (2); JP (1); TW (6); NO (2); IT (1); US (2); HU (1); PE (1); PT (2); IL (3); FR (3); CA (2)