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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 85
- 试验地点
- 30
- 主要终点
- 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)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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 gebasaxturev 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
研究组 & 干预措施
IV Gebasaxturev + Pembrolizumab
Participants receive gebasaxturev 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. Gebasaxturev 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).
干预措施: Gebasaxturev IV (Biological)
IV Gebasaxturev + Pembrolizumab
Participants receive gebasaxturev 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. Gebasaxturev 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).
干预措施: Pembrolizumab (Drug)
ITu Gebasaxturev + Pembrolizumab
Participants receive gebasaxturev 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. Gebasaxturev 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).
干预措施: Gebasaxturev ITu (Biological)
ITu Gebasaxturev + Pembrolizumab
Participants receive gebasaxturev 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. Gebasaxturev 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).
干预措施: Pembrolizumab (Drug)
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).
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
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)
时间窗: Up to ~ 35 months
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.
次要结局
- Overall Survival (OS)(Up to ~ 35 months)
- Progression Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR(Up to ~ 35 months)
- Duration of Response (DOR)(Up to ~ 35 months)
- Objective Response Rate (ORR) Per RECIST 1.1, as Assessed by the Investigator(Up to ~ 35 months)
- Progression Free Survival (PFS) RECIST 1.1, as Assessed by the Investigator(Up to ~ 35 months)
- Duration of Response (DOR) Per RECIST 1.1, as Assessed by the Investigator(Up to ~ 35 months)
- Percentage of Participants Who Experienced an Adverse Event (AE)(Up to ~ 37 months)
- Percentage of Participants Who Discontinued Study Drug Due to an AE(Up to ~ 27 months)