A Phase 2, Randomized, Double-Blind, Placebo- and Active-Comparator-Controlled Clinical Study of V940 (mRNA-4157) Plus Pembrolizumab Versus Placebo Plus Pembrolizumab in Participants With First-Line Advanced Melanoma (INTerpath-012)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 71
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
Researchers want to learn if intismeran autogene with pembrolizumab can stop advanced melanoma from growing or spreading. Melanoma is a type of skin cancer. Advanced means the cancer has spread to other parts of the body and cannot be removed with surgery. A standard (or usual) treatment for advanced melanoma is immunotherapy. Immunotherapy is a treatment that helps the immune system fight cancer. Intismeran autogene is a study treatment designed to help a person's immune system attack their specific cancer. Pembrolizumab is an immunotherapy.
The goal of this study is to learn if people who receive intismeran autogene with pembrolizumab live longer without the cancer growing or spreading than people who receive placebo with pembrolizumab. A placebo looks like the study treatment but has no study treatment in it. Using a placebo helps researchers better understand the effects of a study treatment.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •The main inclusion criteria include but are not limited to the following:
- •Has unresectable and histologically confirmed Stage III or IV cutaneous melanoma per American Joint Committee on Cancer (AJCC) Eighth Edition guidelines.
- •Has been untreated for melanoma except if participant received prior adjuvant or neoadjuvant therapy with targeted therapy or immunotherapy (such as anti-cytotoxic T-lymphocyte-associated protein [CTLA-4], anti-programmed cell death 1 protein [PD-1] therapy or interferon), and only if relapse did not occur within 12 months after treatment discontinuation.
- •Have documentation of serine/threonine-protein kinase B-raf (BRAF) V600-activating mutation status or had BRAF V600 mutation testing per local institutional standards during the screening period (participants with BRAF mutation positive melanoma as well as BRAF wild-type or unknown are eligible).
- •Have the presence of at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by the local site investigator/radiology assessment.
- •Provides tumor tissue (preferably from a metastatic site and, if not available, from the primary tumor) that is suitable for next generation sequencing and biomarker analysis as required for this study.
- •Participants with human immunodeficiency virus (HIV) must have well controlled HIV on antiretroviral therapy (ART).
- •Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization.
- •Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has clinically significant heart failure, defined as New York Heart Association class III or IV, within the past 6 months, unless the disease is well controlled in the opinion of the investigator.
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
- •Has ocular or mucosal melanoma.
- •Received transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 2 weeks of the Screening blood sample (including the blood sample for V940 generation).
- •Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, lymphocyte activation gene 3 [LAG-3], tumor necrosis factor receptors [OX-40 or CD137]), with some exceptions.
- •Received prior systemic anticancer therapy for melanoma before randomization, with some exceptions.
- •Received prior radiotherapy within 2 weeks of start of study intervention or has ongoing radiation related toxicities.
- •Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
- •Received prior treatment with another universal or personalized cancer vaccine.
研究组 & 干预措施
Placebo + Pembrolizumab
Participants will receive placebo via IM injection q3w for up to 9 doses (up to approximately 27 weeks) plus 400 mg of pembrolizumab via IV infusion q6w for up to 17 doses, or for a total treatment duration of up to approximately 2 years, or until disease progression or discontinuation.
干预措施: Placebo (Other)
Placebo + Pembrolizumab
Participants will receive placebo via IM injection q3w for up to 9 doses (up to approximately 27 weeks) plus 400 mg of pembrolizumab via IV infusion q6w for up to 17 doses, or for a total treatment duration of up to approximately 2 years, or until disease progression or discontinuation.
干预措施: Pembrolizumab (Biological)
Intismeran autogene + Pembrolizumab
Participants will receive 1 mg of intismeran autogene via intramuscular (IM) injection every 3 weeks (q3w) for up to 9 doses (up to approximately 27 weeks) plus 400 mg of pembrolizumab via intravenous (IV) infusion every 6 weeks (q6w) for up to 17 doses, or for a total treatment duration of up to approximately 2 years, or until disease progression or discontinuation.
干预措施: Pembrolizumab (Biological)
Intismeran autogene + Pembrolizumab
Participants will receive 1 mg of intismeran autogene via intramuscular (IM) injection every 3 weeks (q3w) for up to 9 doses (up to approximately 27 weeks) plus 400 mg of pembrolizumab via intravenous (IV) infusion every 6 weeks (q6w) for up to 17 doses, or for a total treatment duration of up to approximately 2 years, or until disease progression or discontinuation.
干预措施: Intismeran autogene (Biological)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Up to approximately 36 months
PFS is defined as the time from randomization to the first documented disease progression per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by investigator assessment or death due to any cause, whichever occurs first. Progressive disease (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. PFS per RECIST 1.1 as assessed by investigator will be presented.
次要结局
- Overall Survival (OS)(Up to approximately 6 years)
- Objective Response Rate (ORR)(Up to approximately 6 years)
- Duration of Response (DOR)(Up to approximately 6 years)
- Number of Participants With ≥1 Adverse Event (AE)(Up to approximately 27 months)
- Number of Participants Discontinuing From Study Therapy Due to AE(Up to approximately 24 months)