A Phase 1/2 Study of Combination Immunotherapy and mRNA Vaccine in Subjects With Non-small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
This is an open-label, multicenter, 2-arm study to evaluate the safety and preliminary efficacy of the addition of a vaccine therapy to 1 or 2 checkpoint inhibitors for NSCLC.
Arm A: messenger ribonucleic acid (mRNA) Vaccine [BI 1361849 (formerly CV9202)] + anti-programmed death ligand 1 (PD-L1) antibody [durvalumab]
Arm B: messenger ribonucleic acid (mRNA) Vaccine [BI 1361849] + anti-programmed death ligand 1 (PD-L1) [durvalumab] + anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody [tremelimumab]
The run-in evaluation phase is followed by an expansion phase in which the cohort is expanded to 20 subjects (inclusive of subjects from the run-in).
详细描述
This was a Phase 1/2, open-label, multicenter, 2-arm study to evaluate the safety and preliminary efficacy of the addition of a vaccine therapy to 1 or 2 checkpoint inhibitors in subjects with NSCLC.
Up to 56 subjects were planned for enrollment from up to 8 clinical sites in 2 arms:
Arm A: mRNA Vaccine [BI 1361849 (formerly CV9202)] + anti-PD-L1 antibody [durvalumab]
Arm B: mRNA Vaccine [BI 1361849] + anti-PD-L1 [durvalumab] + anti-CTLA-4 antibody [tremelimumab]
Subjects must have had histologically confirmed metastatic NSCLC. For subjects with known EGFR or ALK/ROS-1 mutations, prior therapy must have included an EGFR tyrosine kinase inhibitor or ALK/ROS-1 inhibitor, respectively. Subjects may have had 1 prior line of anti-PD-1/PD-L1 therapy and must not have had progression at or before 12 weeks after start of the prior anti-PD-1/PD-L1 treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm A: BI 1361849 mRNA Vaccine + durvalumab
The BI 1361849 mRNA vaccine comprises 6 drug product components (F2408 coding for MUC1, F2409 coding for survivin, F2410 coding for NY-ESO-1, F2624 coding for 5T4, F2625 coding for MAGE-C2, and F2626 coding for MAGE-C1), which were provided and administered separately; each component was administered twice, thus there were 12 intradermal administrations of 100 µL (80 µg) each for each dose. The PharmaJet Tropis® device was used for the administration of the BI 1361849 components.
Durvalumab 1500 mg was to be administered as an intravenous (IV) infusion every 4 weeks for 12 cycles; BI 1361849 was to be administered as 14 doses over the 12 cycles.
干预措施: Durvalumab (Drug)
Arm A: BI 1361849 mRNA Vaccine + durvalumab
The BI 1361849 mRNA vaccine comprises 6 drug product components (F2408 coding for MUC1, F2409 coding for survivin, F2410 coding for NY-ESO-1, F2624 coding for 5T4, F2625 coding for MAGE-C2, and F2626 coding for MAGE-C1), which were provided and administered separately; each component was administered twice, thus there were 12 intradermal administrations of 100 µL (80 µg) each for each dose. The PharmaJet Tropis® device was used for the administration of the BI 1361849 components.
Durvalumab 1500 mg was to be administered as an intravenous (IV) infusion every 4 weeks for 12 cycles; BI 1361849 was to be administered as 14 doses over the 12 cycles.
干预措施: BI 1361849 (Biological)
Arm A: BI 1361849 mRNA Vaccine + durvalumab
The BI 1361849 mRNA vaccine comprises 6 drug product components (F2408 coding for MUC1, F2409 coding for survivin, F2410 coding for NY-ESO-1, F2624 coding for 5T4, F2625 coding for MAGE-C2, and F2626 coding for MAGE-C1), which were provided and administered separately; each component was administered twice, thus there were 12 intradermal administrations of 100 µL (80 µg) each for each dose. The PharmaJet Tropis® device was used for the administration of the BI 1361849 components.
Durvalumab 1500 mg was to be administered as an intravenous (IV) infusion every 4 weeks for 12 cycles; BI 1361849 was to be administered as 14 doses over the 12 cycles.
干预措施: PharmaJet Tropis® device (Device)
Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab
The BI 1361849 mRNA vaccine comprises 6 drug product components (F2408 coding for MUC1, F2409 coding for survivin, F2410 coding for NY-ESO-1, F2624 coding for 5T4, F2625 coding for MAGE-C2, and F2626 coding for MAGE-C1), which were provided and administered separately; each component was administered twice, thus there were 12 intradermal administrations of 100 µL (80 µg) each for each dose. The PharmaJet Tropis® device was used for the administration of the BI 1361849 components.
Durvalumab 1500 mg was to be administered as an intravenous (IV) infusion every 4 weeks for 12 cycles; tremelimumab 75 mg was to be administered as an intravenous (IV) infusion every 4 weeks for the first 4 cycles (Arm B only); BI 1361849 was to be administered as 14 doses over the 12 cycles.
干预措施: Durvalumab (Drug)
Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab
The BI 1361849 mRNA vaccine comprises 6 drug product components (F2408 coding for MUC1, F2409 coding for survivin, F2410 coding for NY-ESO-1, F2624 coding for 5T4, F2625 coding for MAGE-C2, and F2626 coding for MAGE-C1), which were provided and administered separately; each component was administered twice, thus there were 12 intradermal administrations of 100 µL (80 µg) each for each dose. The PharmaJet Tropis® device was used for the administration of the BI 1361849 components.
Durvalumab 1500 mg was to be administered as an intravenous (IV) infusion every 4 weeks for 12 cycles; tremelimumab 75 mg was to be administered as an intravenous (IV) infusion every 4 weeks for the first 4 cycles (Arm B only); BI 1361849 was to be administered as 14 doses over the 12 cycles.
干预措施: Tremelimumab (Drug)
Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab
The BI 1361849 mRNA vaccine comprises 6 drug product components (F2408 coding for MUC1, F2409 coding for survivin, F2410 coding for NY-ESO-1, F2624 coding for 5T4, F2625 coding for MAGE-C2, and F2626 coding for MAGE-C1), which were provided and administered separately; each component was administered twice, thus there were 12 intradermal administrations of 100 µL (80 µg) each for each dose. The PharmaJet Tropis® device was used for the administration of the BI 1361849 components.
Durvalumab 1500 mg was to be administered as an intravenous (IV) infusion every 4 weeks for 12 cycles; tremelimumab 75 mg was to be administered as an intravenous (IV) infusion every 4 weeks for the first 4 cycles (Arm B only); BI 1361849 was to be administered as 14 doses over the 12 cycles.
干预措施: BI 1361849 (Biological)
Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab
The BI 1361849 mRNA vaccine comprises 6 drug product components (F2408 coding for MUC1, F2409 coding for survivin, F2410 coding for NY-ESO-1, F2624 coding for 5T4, F2625 coding for MAGE-C2, and F2626 coding for MAGE-C1), which were provided and administered separately; each component was administered twice, thus there were 12 intradermal administrations of 100 µL (80 µg) each for each dose. The PharmaJet Tropis® device was used for the administration of the BI 1361849 components.
Durvalumab 1500 mg was to be administered as an intravenous (IV) infusion every 4 weeks for 12 cycles; tremelimumab 75 mg was to be administered as an intravenous (IV) infusion every 4 weeks for the first 4 cycles (Arm B only); BI 1361849 was to be administered as 14 doses over the 12 cycles.
干预措施: PharmaJet Tropis® device (Device)
结局指标
主要结局
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
时间窗: up to 15 months
Adverse events (AEs) were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 20.0 and classified by MedDRA system organ class (SOC) and preferred term. The severity was assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. AEs were reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through 90 days after the last dose of study treatment. TEAEs are AEs that occurred or worsened in severity after administration of the first dose of study treatment. For each arm, the first 6 subjects were evaluated for dose limiting toxicities (DLTs). Deaths within the AE Reporting Period included all deaths that occurred during the study treatment period, or up to 90 days after the administration of the last dose of study drug or initiation of a new treatment.
次要结局
- Number of Subjects Without Progression at 8 and 24 Weeks by irRECIST(up to 24 weeks)
- Median PFS by RECIST 1.1 as Estimated Using the Kaplan-Meier Method(up to 15 months)
- Number of Subjects Without Progression at 8 and 24 Weeks by RECIST 1.1(up to 24 weeks)
- Median PFS by irRECIST as Estimated Using the Kaplan-Meier Method(up to 15 months)
- Number of Subjects With Objective Responses at 8 and 24 Weeks By irRECIST(up to 24 weeks)
- Duration of Response (DoR) by irRECIST(Up tp 15 months)
- Number of Subjects With Best Overall Tumor Response By RECIST 1.1(up to 15 months)
- Number of Subjects With Objective Responses at 8 and 24 Weeks By RECIST 1.1(up to 24 weeks)
- Number of Subjects With Best Overall Tumor Response By irRECIST(up to 15 months)
- Duration of Response (DoR) By RECIST 1.1(up to 15 months)
- Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method(up to October 29, 2021)