An Open Label, Multi-Center, Dose Escalation/Expansion, Phase 1/1b Study of IMU-201, a B-Cell Immunotherapy as Monotherapy or in Combination With Atezolizumab With or Without Chemotherapy, in Adults With Non- Small Cell Lung Cancer (IMPrinter)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 6
- 主要终点
- Overall response rate (ORR) (Dose Expansion)
研究概览
简要总结
An Open Label, Multi-Center, Dose Escalation/Expansion, Phase 1/1b Study of IMU 201 (PD1-Vaxx), a B-Cell Immunotherapy as monotherapy or in combination with atezolizumab with or without chemotherapy, in Adults with Non-Small Cell Lung Cancer (IMPrinter).
详细描述
Investigational Medicinal Product, IMU-201, consists of drug substance, APi2568, which is a B-cell epitope (amino acids 92-110 from PD-1) linked to a promiscuous T-cell epitope (amino acid residues 288-302 from measles virus fusion protein) via a 4-amino acid linker (Gly-Pro-Ser-Leu), and combined with Water for Injection (WFI) forms the drug product, IMU-201, which becomes PD1-Vaxx when emulsified with excipient Montanide ISA 720 VG.
It is hypothesized that a polyclonal induced B-cell antibody response will be more effective or as effective with improved safety over current monoclonal antibody therapy.
This phase 1/1b study is an open-label dose escalation/dose expansion study designed to assess the safety, tolerability, immunogenicity and efficacy of IMU-201 (PD1-Vaxx). Phase 1 monotherapy dose-escalation of IMU-201 (PD1-Vaxx), will enroll approximately 9-18 patients and establish the optimal monotherapy biological dose (mBOD). Once established, the dose cohort will be expanded to enroll additional 10 patients at the mBOD dose level. Phase 1b, a combination dose-escalation of IMU-201 (PD1-Vaxx) with atezolizumab and with or without chemotherapy, will enroll approximately 18-36 patients and establish the optimal combotherapy biological dose (cBOD). Once established, the dose cohort will be expanded to enroll additional 30 patients at the cBOD dose level.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Age ≥ 18 years with histologically confirmed non-small-cell lung cancer (NSCLC) tumor stage IIIb not eligible for definitive treatment or stage IV
- •Prior treatment criterion for Monotherapy dose escalation and expansion: progressed on/after prior PD-1/PD-L1 containing regimen
- •Prior treatment criteria for Combination dose escalation arms:
- •IMU-201 + atezolizumab, patients naïve to prior treatment or progressed on/after prior PD-1/PD-L1 containing regimen
- •IMU-201 + atezolizumab + chemotherapy, patient naïve to prior treatment naive
- •Prior treatment criteria for Combination dose expansion arms:
- •IMU-201 + atezolizumab, progressed on/after prior PD-1/PD-L1 containing regimen
- •IMU-201 + atezolizumab, patients naïve to prior treatment
- •IMU-201 + atezolizumab + chemotherapy, patients naïve to prior treatment
- •PD-L1 expression criteria (testing by 22C3, SP142, or SP263) for Monotherapy dose escalation and expansion: TPS/TC ≥ 50% or IC ≥ 10%. Patients with PD-L1 TPS/TC<50% or IC<10% expression may be included with agreement of Sponsor
- •PD-L1 expression criteria for Combination dose escalation arms:
- •IMU-201 + atezolizumab, TPS/TC ≥ 50% or IC ≥ 10%
- •IMU-201 + atezolizumab + chemotherapy, independent of PD-L1 expression
- •PD-L1 expression criteria for Combination dose expansion arms:
- •IMU-201 + atezolizumab, TPS/TC ≥ 50% or IC ≥ 10%
- •IMU-201 + atezolizumab, TPS/TC ≥ 50% or IC ≥ 10%
- •IMU-201 + atezolizumab + chemotherapy, independent of PD-L1 expression
- •Life expectancy of at least 12 weeks in the opinion of the Investigator
- •Zubrod/ECOG score performance status 0-1
- •At least one measurable lesion as defined by RECIST 1.1 criteria.
- •Adequate hematologic, liver, and renal function
排除标准
- •Prior therapy for advanced NSCLC within 3 weeks prior to Day 1;
- •Continuous systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 2 weeks prior to first dose of study treatment.;
- •Any previous grade 3 or higher toxicity to a PD-1 inhibitor or PD-L1 inhibitor;
- •Has a history of (non-infectious) pneumonitis/interstitial lung disease that required treatment with immunosuppressive agents or has current pneumonitis/interstitial lung disease;
- •Known brain metastases requiring steroid treatment, or signs and symptoms indicating suspected brain metastases;
- •Current or previous history of auto-immune disease;
- •NSCLC expressing epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), B-Raf proto-oncogene (BRAF) or ROS proto-oncogene 1 (ROS1) mutations who have not received appropriate therapies targeting these mutations and progress (if treatments are not available, patients who have NOT received appropriate therapies may be enrolled);
- •Prior organ transplant;
- •Concurrent active malignancy except for adequately controlled limited basal cell carcinoma of the skin;
- •History of uncontrolled seizures, central nervous disorders, or psychiatric disability judged by the Investigator to be clinically significant and precluding informed consent, participation in the study, or adversely affecting compliance to study drugs;
- •Active infection requiring intravenous antibiotics;
- •Known history of human immunodeficiency virus (HIV) infection or Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV Ribonucleic acid (RNA) [qualitative] is detected) infection;
- •Major surgery within 4 weeks prior to study entry. Minor surgery (excluding diagnostic biopsy) within 1 week prior to study entry;
- •Any vaccination within 2 weeks prior to starting study treatment;
- •Treatment with any investigational drug or participation in another investigational study within 3 weeks prior to first IMU-201 dose.
研究组 & 干预措施
Dose Escalation: Monotherapy Cohort 1
10 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
干预措施: IMU-201 (administered as PD1-Vaxx) - Regimen 1 (Biological)
Dose Escalation: Monotherapy Cohort 2
50 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
干预措施: IMU-201 (administered as PD1-Vaxx) - Regimen 1 (Biological)
Dose Escalation: Monotherapy Cohort 3
100 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
干预措施: IMU-201 (administered as PD1-Vaxx) - Regimen 1 (Biological)
Dose Expansion Monotherapy
mOBD (TBD) dose IMU-201 as a 0.5 mL PD1-Vaxx injection Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
干预措施: IMU-201 (administered as PD1-Vaxx) - Regimen 1 (Biological)
Dose Escalation Arm 1: Combination with atezolizumab Cohort 1
10 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg Naïve to ICI or Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
干预措施: IMU-201 (administered as PD1-Vaxx) - Regimen 2 (Biological)
Dose Escalation Arm 1: Combination with atezolizumab Cohort 1
10 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg Naïve to ICI or Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
干预措施: Atezolizumab (Drug)
Dose Escalation Arm 1: Combination with atezolizumab Cohort 2
50 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg Naïve to ICI or Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
干预措施: IMU-201 (administered as PD1-Vaxx) - Regimen 2 (Biological)
Dose Escalation Arm 1: Combination with atezolizumab Cohort 2
50 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg Naïve to ICI or Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
干预措施: Atezolizumab (Drug)
Dose Escalation Arm 1: Combination with atezolizumab Cohort 3
Cohort 3: 100 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg Naïve to ICI or Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
干预措施: IMU-201 (administered as PD1-Vaxx) - Regimen 2 (Biological)
Dose Escalation Arm 1: Combination with atezolizumab Cohort 3
Cohort 3: 100 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg Naïve to ICI or Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
干预措施: Atezolizumab (Drug)
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 1
10 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg and SOC chemotherapy Naïve to ICI, Any PD-L1 Level
干预措施: IMU-201 (administered as PD1-Vaxx) - Regimen 3 (Biological)
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 1
10 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg and SOC chemotherapy Naïve to ICI, Any PD-L1 Level
干预措施: Atezolizumab (Drug)
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 1
10 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg and SOC chemotherapy Naïve to ICI, Any PD-L1 Level
干预措施: Standard of care chemotherapy (Drug)
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 2
50 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg and SOC chemotherapy Naïve to ICI, Any PD-L1 Level
干预措施: IMU-201 (administered as PD1-Vaxx) - Regimen 3 (Biological)
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 2
50 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg and SOC chemotherapy Naïve to ICI, Any PD-L1 Level
干预措施: Atezolizumab (Drug)
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 2
50 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg and SOC chemotherapy Naïve to ICI, Any PD-L1 Level
干预措施: Standard of care chemotherapy (Drug)
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 3
100 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg and SOC chemotherapy Naïve to ICI, Any PD-L1 Level
干预措施: IMU-201 (administered as PD1-Vaxx) - Regimen 3 (Biological)
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 3
100 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg and SOC chemotherapy Naïve to ICI, Any PD-L1 Level
干预措施: Atezolizumab (Drug)
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 3
100 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg and SOC chemotherapy Naïve to ICI, Any PD-L1 Level
干预措施: Standard of care chemotherapy (Drug)
Dose Expansion Arm 1: Combination with atezolizumab
cOBD (TBD) dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
干预措施: IMU-201 (administered as PD1-Vaxx) - Regimen 2 (Biological)
Dose Expansion Arm 1: Combination with atezolizumab
cOBD (TBD) dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
干预措施: Atezolizumab (Drug)
Dose Expansion Arm 2: Combination with atezolizumab
cOBD (TBD) dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg Naïve to ICI, TPS/TC ≥50% or IC ≥10%
干预措施: IMU-201 (administered as PD1-Vaxx) - Regimen 2 (Biological)
Dose Expansion Arm 2: Combination with atezolizumab
cOBD (TBD) dose IMU-201 as a 0.5 mL PD1-Vaxx injection with atezolizumab 840 mg Naïve to ICI, TPS/TC ≥50% or IC ≥10%
干预措施: Atezolizumab (Drug)
Dose Expansion Arm 3: Combination with atezolizumab and chemotherapy
cOBD (TBD) dose IMU-201 as a 05 mL PD1-Vaxx injection with atezolizumab 840 mg and SOC chemotherapy Naïve to ICI, Any PD-L1 Level
干预措施: IMU-201 (administered as PD1-Vaxx) - Regimen 3 (Biological)
Dose Expansion Arm 3: Combination with atezolizumab and chemotherapy
cOBD (TBD) dose IMU-201 as a 05 mL PD1-Vaxx injection with atezolizumab 840 mg and SOC chemotherapy Naïve to ICI, Any PD-L1 Level
干预措施: Atezolizumab (Drug)
Dose Expansion Arm 3: Combination with atezolizumab and chemotherapy
cOBD (TBD) dose IMU-201 as a 05 mL PD1-Vaxx injection with atezolizumab 840 mg and SOC chemotherapy Naïve to ICI, Any PD-L1 Level
干预措施: Standard of care chemotherapy (Drug)
结局指标
主要结局
Overall response rate (ORR) (Dose Expansion)
时间窗: Baseline to documented progressive disease (Approximately 15 months)
Efficacy of IMU-201 will be evaluated by overall response rate at OBD of IMU-201 measured as the proportion of participants with a best overall response of complete or partial response.
Safety and tolerability of IMU-201 graded per terminology criteria for adverse events (CTCAE) version 5.00 (Dose Escalation)
时间窗: Baseline to Day 29
Safety and Tolerability Measures include: Frequency of adverse events (AEs) graded per terminology criteria for adverse events (CTCAE) version 5.00.
Identify Optimal Biological Dose (OBD) with safety/tolerability graded per terminology criteria for adverse events (CTCAE) version 5.00 and Immuogenicity (Dose Escalation).
时间窗: Baseline to Day 43
Safety and Tolerability Measures: Adverse events (AEs); dose-limiting toxicities (DLTs) graded per terminology criteria for adverse events (CTCAE) version 5.00. Immunogenicity data for IMU-201 includes PD-1 specific antibody (IgG) titers.
次要结局
- Overall response rate (ORR) (Dose Escalation)(Baseline to documented progressive disease (Approximately 15 Months))
- Overall survival (OS) (Dose Escalation/Expansion)(Baseline to death from any cause (Approximately 15 Months))
- Duration of response (DOR) (Dose Escalation/Expansion)(From date of earliest CR or PR until the date of first documented progression or death from any cause (Approximately 15 Months))
- Progression free survival (PFS) (Dose Escalation/Expansion)(Baseline to documented progressive disease or death due to any cause (Approximately 15 Months))