A Study of IMU-201 (PD1-Vaxx), a B-Cell Immunotherapy, in Adults with Non-Small Cell Lung Cancer

Phase 1

Active, not recruiting

• Conditions: Non Small Cell Lung Cancer; Non Small Cell Lung Cancer Stage IIIB; Non-small Cell Lung Cancer Stage IV; Large Cell Carcinoma Lung; Squamous Non-small-cell Lung Cancer; Adenocarcinoma Lung
• Interventions: Biological: IMU-201 (administered as PD1-Vaxx) - Regimen 1; Biological: IMU-201 (administered as PD1-Vaxx) - Regimen 2; Biological: IMU-201 (administered as PD1-Vaxx) - Regimen 3; Drug: Atezolizumab; Drug: Standard of care chemotherapy

• Registration Number: NCT04432207
• Lead Sponsor: Imugene Limited

Brief Summary

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).

Detailed Description

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.

Study Timeline

• Study First Submitted: 2020-05-10
• Study First Submitted QC: 2020-06-11
• Study First Posted: 2020-06-16
• Study Start: 2020-11-30
• Status Verified: 2024-01
• Primary Completion: 2024-11
• Last Update Submitted: 2024-11-05
• Last Update Posted: 2024-11-07
• Study Completion: 2025-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Age ≥ 18 years with histologically confirmed non-small-cell lung cancer (NSCLC) tumor stage IIIb not eligible for definitive treatment or stage IV

2. Prior treatment criterion for Monotherapy dose escalation and expansion: progressed on/after prior PD-1/PD-L1 containing regimen

3. Prior treatment criteria for Combination dose escalation arms:

   1. IMU-201 + atezolizumab, patients naïve to prior treatment or progressed on/after prior PD-1/PD-L1 containing regimen
   2. IMU-201 + atezolizumab + chemotherapy, patient naïve to prior treatment naive

4. Prior treatment criteria for Combination dose expansion arms:

   1. IMU-201 + atezolizumab, progressed on/after prior PD-1/PD-L1 containing regimen
   2. IMU-201 + atezolizumab, patients naïve to prior treatment
   3. IMU-201 + atezolizumab + chemotherapy, patients naïve to prior treatment

5. 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

6. PD-L1 expression criteria for Combination dose escalation arms:

   1. IMU-201 + atezolizumab, TPS/TC ≥ 50% or IC ≥ 10%
   2. IMU-201 + atezolizumab + chemotherapy, independent of PD-L1 expression

7. PD-L1 expression criteria for Combination dose expansion arms:

   1. IMU-201 + atezolizumab, TPS/TC ≥ 50% or IC ≥ 10%
   2. IMU-201 + atezolizumab, TPS/TC ≥ 50% or IC ≥ 10%
   3. IMU-201 + atezolizumab + chemotherapy, independent of PD-L1 expression

8. Life expectancy of at least 12 weeks in the opinion of the Investigator

9. Zubrod/ECOG score performance status 0-1

10. At least one measurable lesion as defined by RECIST 1.1 criteria.

11. Adequate hematologic, liver, and renal function

Exclusion Criteria

1. Prior therapy for advanced NSCLC within 3 weeks prior to Day 1;
2. 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.;
3. Any previous grade 3 or higher toxicity to a PD-1 inhibitor or PD-L1 inhibitor;
4. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required treatment with immunosuppressive agents or has current pneumonitis/interstitial lung disease;
5. Known brain metastases requiring steroid treatment, or signs and symptoms indicating suspected brain metastases;
6. Current or previous history of auto-immune disease;
7. 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);
8. Prior organ transplant;
9. Concurrent active malignancy except for adequately controlled limited basal cell carcinoma of the skin;
10. 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;
11. Active infection requiring intravenous antibiotics;
12. 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;
13. Major surgery within 4 weeks prior to study entry. Minor surgery (excluding diagnostic biopsy) within 1 week prior to study entry;
14. Any vaccination within 2 weeks prior to starting study treatment;
15. Treatment with any investigational drug or participation in another investigational study within 3 weeks prior to first IMU-201 dose.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation: Monotherapy Cohort 1	IMU-201 (administered as PD1-Vaxx) - Regimen 1	10 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
Dose Escalation: Monotherapy Cohort 3	IMU-201 (administered as PD1-Vaxx) - Regimen 1	100 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
Dose Escalation Arm 1: Combination with atezolizumab Cohort 2	IMU-201 (administered as PD1-Vaxx) - Regimen 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%
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 3	Standard of care chemotherapy	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
Dose Expansion Arm 2: Combination with atezolizumab	IMU-201 (administered as PD1-Vaxx) - Regimen 2	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%
Dose Escalation Arm 1: Combination with atezolizumab Cohort 1	IMU-201 (administered as PD1-Vaxx) - Regimen 2	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%
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 2	IMU-201 (administered as PD1-Vaxx) - Regimen 3	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
Dose Expansion Arm 3: Combination with atezolizumab and chemotherapy	IMU-201 (administered as PD1-Vaxx) - Regimen 3	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
Dose Expansion Arm 3: Combination with atezolizumab and chemotherapy	Standard of care 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
Dose Escalation Arm 1: Combination with atezolizumab Cohort 3	IMU-201 (administered as PD1-Vaxx) - Regimen 2	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%
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 2	Standard of care chemotherapy	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
Dose Expansion Arm 1: Combination with atezolizumab	IMU-201 (administered as PD1-Vaxx) - Regimen 2	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%
Dose Escalation: Monotherapy Cohort 2	IMU-201 (administered as PD1-Vaxx) - Regimen 1	50 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
Dose Expansion Monotherapy	IMU-201 (administered as PD1-Vaxx) - Regimen 1	mOBD (TBD) dose IMU-201 as a 0.5 mL PD1-Vaxx injection Progressed on/after ICI, TPS/TC ≥50% or IC ≥10%
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 1	Standard of care chemotherapy	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
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 3	IMU-201 (administered as PD1-Vaxx) - Regimen 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
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 1	IMU-201 (administered as PD1-Vaxx) - Regimen 3	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
Dose Escalation Arm 1: Combination with atezolizumab Cohort 1	Atezolizumab	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%
Dose Escalation Arm 1: Combination with atezolizumab Cohort 3	Atezolizumab	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%
Dose Escalation Arm 1: Combination with atezolizumab Cohort 2	Atezolizumab	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%
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 2	Atezolizumab	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
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 1	Atezolizumab	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
Dose Escalation Arm 2: Combination with atezolizumab and chemotherapy Cohort 3	Atezolizumab	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
Dose Expansion Arm 1: Combination with atezolizumab	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%
Dose Expansion Arm 2: Combination with atezolizumab	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%
Dose Expansion Arm 3: Combination with atezolizumab and chemotherapy	Atezolizumab	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

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR) (Dose Expansion)	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)	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).	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.

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR) (Dose Escalation)	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.
Overall survival (OS) (Dose Escalation/Expansion)	Baseline to death from any cause (Approximately 15 Months)	Efficacy of IMU-201 will be evaluated by overall survival at OBD of IMU-201.
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)	Efficacy of IMU-201 will be evaluated by duration of response at OBD of IMU-201.
Progression free survival (PFS) (Dose Escalation/Expansion)	Baseline to documented progressive disease or death due to any cause (Approximately 15 Months)	Efficacy of IMU-201 will be evaluated by progression free survival at OBD of IMU-201.

Trial Locations

Locations (6)

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Mayo Clinic; 🇺🇸 Phoenix, Arizona, United States

Chris O'Brien Lifehouse; 🇦🇺 Camperdown, New South Wales, Australia

Ohio State University Medical Center; 🇺🇸 Columbus, Ohio, United States

Cabrini Malvern Hospital; 🇦🇺 Melbourne, Victoria, Australia

Macquarie University; 🇦🇺 Macquarie, New South Wales, Australia