A Phase 3, Randomized, Double-blind, Placebo- and Active-Comparator-Controlled Clinical Study of Adjuvant V940 (mRNA-4157) Plus Pembrolizumab Versus Adjuvant Placebo Plus Pembrolizumab in Participants With Resected Stage II, IIIA, IIIB (N2) Non-small Cell Lung Cancer (INTerpath-002)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 868
- 试验地点
- 737
- 主要终点
- Disease- Free Survival (DFS)
研究概览
简要总结
The goal of this study is to evaluate intismeran autogene plus pembrolizumab versus placebo plus pembrolizumab for the adjuvant treatment of margin negative, completely resected Stage II, IIIA, IIIB (with nodal involvement [N2]) non-small cell lung cancer (NSCLC). The primary hypothesis is that intismeran autogene plus pembrolizumab is superior to placebo plus pembrolizumab with respect to disease-free survival (DFS) as assessed by the investigator.
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
- Double (Participant, Investigator)
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 undergone margin negative, completely resected non-small cell lung cancer (NSCLC), and has pathological Stage II, IIIA, IIIB (N2) squamous or nonsquamous tumor, node, metastasis (TNM) staging per American Joint Committee on Cancer (AJCC) Eighth Edition guidelines.
- •Has no evidence of disease before randomization.
- •Has received at least one dose of adjuvant treatment with standard of care platinum doublet chemotherapy.
- •No more than 24 weeks have elapsed between surgical resection of curative intent and the first dose of pembrolizumab.
- •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.
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy (ART).
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Diagnosis of small cell lung cancer (SCLC) or, for mixed tumors, presence of small cell elements, or has a neuroendocrine tumor with large cell components or a sarcomatoid carcinoma.
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
- •Received prior neoadjuvant therapy for their current NSCLC diagnosis.
- •Received or is a candidate to receive radiotherapy for their current NSCLC diagnosis.
- •Received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-PD-ligand 1 (L1), or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
- •Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
- •Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
- •Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
- •Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication.
- •Known additional malignancy that is progressing or has required active treatment within the past 5 years.
- •Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.
- •History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- •Active infection requiring systemic therapy.
研究组 & 干预措施
Placebo + Pembrolizumab
Participants will receive intismeran autogene-matched placebo via IM injection once every 3 weeks for 9 doses PLUS 400 mg of pembrolizumab via IV infusion once every 6 weeks for up to 9 doses until disease recurrence or unacceptable toxicity or for a total treatment duration of up to approximately 1 year, whichever is sooner.
干预措施: Placebo (Other)
Placebo + Pembrolizumab
Participants will receive intismeran autogene-matched placebo via IM injection once every 3 weeks for 9 doses PLUS 400 mg of pembrolizumab via IV infusion once every 6 weeks for up to 9 doses until disease recurrence or unacceptable toxicity or for a total treatment duration of up to approximately 1 year, whichever is sooner.
干预措施: Pembrolizumab (Biological)
Intismeran autogene + Pembrolizumab
Participants will receive 1 mg of intismeran autogene via intramuscular (IM) injection once every 3 weeks for 9 doses PLUS 400 mg of pembrolizumab via intravenous (IV) infusion once every 6 weeks for up to 9 doses until disease recurrence or unacceptable toxicity or for a total treatment duration of up to approximately 1 year, whichever is sooner.
干预措施: Intismeran autogene (Biological)
Intismeran autogene + Pembrolizumab
Participants will receive 1 mg of intismeran autogene via intramuscular (IM) injection once every 3 weeks for 9 doses PLUS 400 mg of pembrolizumab via intravenous (IV) infusion once every 6 weeks for up to 9 doses until disease recurrence or unacceptable toxicity or for a total treatment duration of up to approximately 1 year, whichever is sooner.
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Disease- Free Survival (DFS)
时间窗: Up to ~78 months
DFS is defined as the time from randomization to any recurrence (local, locoregional, regional or distant), occurrence of new primary NSCLC, as assessed by the investigator, or death due to any cause, whichever occurs first.
次要结局
- Distant Metastasis-Free Survival (DMFS)(Up to ~12 years)
- Overall Survival (OS)(Up to ~12 years)
- Number of Participants Who Experience an Adverse Event (AE)(Up to ~15 months)
- Lung Cancer Specific Survival (LCSS)(Up to ~12 years)
- Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score(Baseline and up to ~12 years)
- Change from Baseline in the EORTC QLQ-C30 Dyspnea (Item 8) Score on the EORTC QLQ-C30(Baseline and up to ~12 years)
- Change from Baseline in the EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30(Baseline and up to ~12 years)
- Change from Baseline in the EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score on the EORTC QLQ-C30(Baseline and up to ~12 years)
- Change from Baseline in the EORTC QLQ-LC24 Chest Pain (Item 40) Score on the EORTC QLQ-LC24(Baseline and up to ~12 years)
- Number of Participants Who Discontinue Study Treatment Due to an AE(Up to ~12 months)
- Change from Baseline in the EORTC QLQ-Lung Cancer Questionnaire (LC24) Coughing (Items 31 and 52) Combined Score on the EORTC QLQ-LC24(Baseline and up to ~12 years)