A Phase 3 Randomized Double-blind Study of Adjuvant Pembrolizumab With or Without V940 in Participants With Resectable Stage II to IIIB (N2) NSCLC Not Achieving pCR After Receiving Neoadjuvant Pembrolizumab With Platinum-based Doublet Chemotherapy (INTerpath-009)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 680
- 试验地点
- 450
- 主要终点
- Disease-Free Survival (DFS)
研究概览
简要总结
The goal of this study is to learn if people who receive intismeran autogene and pembrolizumab after surgery are cancer-free longer than people who receive placebo and pembrolizumab. Researchers want to know if giving intismeran autogene and pembrolizumab after surgery can help prevent the cancer from coming back in people with non-small cell lung cancer (NSCLC) whose tumors did not respond completely to treatment before surgery (neoadjuvant 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
- 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 histologically/cytologically confirmed diagnosis of previously untreated and pathologically confirmed resectable clinical Stage II, IIIA, or IIIB (N2) non-small cell lung cancer (NSCLC) [American Joint Committee on Cancer (AJCC) 8th Edition]
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before the first dose of study intervention
- •Participants who have not achieved a pathological complete response (pCR) following completion of neoadjuvant chemotherapy and pembrolizumab followed by surgery will be eligible
- •Confirmation that epidermal growth factor receptor (EGFR)-directed therapy is not indicated as primary therapy (documentation of absence of tumor-activating EGFR mutations [eg, DEL19 or L858R])
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral 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:
- •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, or a pancoast tumor
- •Documentation by local test report indicating presence of anaplastic lymphoma kinase (ALK) gene rearrangements
- •Received prior neoadjuvant therapy for their current NSCLC diagnosis
- •Received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell-death ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein [CTLA-4], OX-40, CD137)
- •Received prior systemic anticancer therapy including investigational agents other than what is specified in this protocol
- •Received prior treatment with a cancer vaccine
- •Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
- •Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
研究组 & 干预措施
Pembrolizumab + Intismeran autogene
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via intravenous (IV) infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC] 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS intismeran autogene 1 mg via intramuscular (IM) injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
干预措施: Paclitaxel (Drug)
Pembrolizumab + Intismeran autogene
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via intravenous (IV) infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC] 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS intismeran autogene 1 mg via intramuscular (IM) injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
干预措施: Intismeran autogene (Biological)
Pembrolizumab + Intismeran autogene
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via intravenous (IV) infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC] 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS intismeran autogene 1 mg via intramuscular (IM) injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
干预措施: Cisplatin (Drug)
Pembrolizumab + Placebo
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via IV infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin AUC 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS matching placebo via IM injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
干预措施: Cisplatin (Drug)
Pembrolizumab + Placebo
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via IV infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin AUC 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS matching placebo via IM injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
干预措施: Placebo (Other)
Pembrolizumab + Placebo
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via IV infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin AUC 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS matching placebo via IM injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Placebo
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via IV infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin AUC 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS matching placebo via IM injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
干预措施: Pemetrexed (Drug)
Pembrolizumab + Placebo
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via IV infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin AUC 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS matching placebo via IM injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
干预措施: Paclitaxel (Drug)
Pembrolizumab + Intismeran autogene
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via intravenous (IV) infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC] 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS intismeran autogene 1 mg via intramuscular (IM) injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Intismeran autogene
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via intravenous (IV) infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC] 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS intismeran autogene 1 mg via intramuscular (IM) injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
干预措施: Carboplatin (Drug)
Pembrolizumab + Intismeran autogene
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via intravenous (IV) infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC] 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS intismeran autogene 1 mg via intramuscular (IM) injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
干预措施: Pemetrexed (Drug)
Pembrolizumab + Placebo
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via IV infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin AUC 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS matching placebo via IM injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
干预措施: Carboplatin (Drug)
Pembrolizumab + Intismeran autogene
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via intravenous (IV) infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC] 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS intismeran autogene 1 mg via intramuscular (IM) injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
干预措施: Gemcitabine (Drug)
Pembrolizumab + Placebo
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via IV infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin AUC 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS matching placebo via IM injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Disease-Free Survival (DFS)
时间窗: Up to ~97 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
- Overall Survival (OS)(Up to ~129 months)
- Distant Metastasis-Free Survival (DMFS)(Up to ~129 months)
- Disease-Free Survival 2 (DFS2)(Up to ~129 months)
- Lung Cancer Specific Survival (LCSS)(Up to ~129 months)
- Number of participants with ≥1 adverse event (AE)(Up to ~129 months)
- 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)(Baseline and up to ~129 months)
- Change from Baseline in the EORTC QLQ-C30 Physical Functioning (Items 1-5)(Baseline and up to ~129 months)
- Change from Baseline in the EORTC QLQ-C30 Role Functioning (Items 6 and 7)(Baseline and up to ~129 months)
- Number of participants discontinuing from study therapy due to AE(s)(Up to ~129 months)