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

Non Small Cell Lung Cancer Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04432207
• Other study ID #: IMU.201.101
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 30, 2020
• Est. completion date: March 2026

Study information

• Verified date: January 2024
• Source: Imugene Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: March 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma Lung
• Adenocarcinoma of Lung
• Carcinoma, Large Cell
• Carcinoma, Non-Small-Cell Lung
• Large Cell Carcinoma Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer
• Non Small Cell Lung Cancer Stage IIIB
• Non-small Cell Lung Cancer Stage IV
• Squamous Non-small-cell Lung Cancer

Intervention

Biological:
• IMU-201 (administered as PD1-Vaxx) - Regimen 1
IMU-201 consists of APi2568 (lyophilized IMU-201) dissolved in WFI and emulsified with the adjuvant (Montanide ISA 720 VG) to produce PD1-Vaxx. IMU-201 will be administered as PD1-Vaxx intramuscularly into the deltoid region of the upper arm on Days 1, 15, 29, 64 and thereafter every 63 days until discontinuation from study.
• IMU-201 (administered as PD1-Vaxx) - Regimen 2
IMU-201 consists of APi2568 (lyophilized IMU-201) dissolved in WFI and emulsified with the adjuvant (Montanide ISA 720 VG) to produce PD1-Vaxx. IMU-201 will be administered as PD1-Vaxx intramuscularly into the deltoid region of the upper arm on Days 1, 15, 29, 57 and thereafter every subsequent 63 days until discontinuation from study.
• IMU-201 (administered as PD1-Vaxx) - Regimen 3
IMU-201 consists of APi2568 (lyophilized IMU-201) dissolved in WFI and emulsified with the adjuvant (Montanide ISA 720 VG) to produce PD1-Vaxx. IMU-201 will be administered as PD1-Vaxx intramuscularly into the deltoid region of the upper arm on Days 1, 15, 29, 57 and thereafter every 56 or 63 days until discontinuation from study.

Drug:
• Atezolizumab
Atezolizumab will be administered every 2 weeks (Q2W) starting Day 15 until discontinuation from study.
• Standard of care chemotherapy
Chemotherapy to be administered according to the prescribing information.

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Macquarie University	Macquarie	New South Wales
Australia	Cabrini Malvern Hospital	Melbourne	Victoria
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Mayo Clinic	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Imugene Limited

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory Outcome: Humoral immunogenicity of IMU-201 (Dose Escalation/Expansion)	Humoral immunogenicity evaluated by PD-1 specific antibodies (IgG, IgM).	Baseline to documented progressive disease (Approximately 15 Months)
Other	Exploratory Outcome: Cellular immunogenicity of IMU-201 (Dose Escalation/Expansion)	Cellular immunogenicity evaluated by vaccine-specific cytokine levels as well as analysis of regulatory and effector T and B cells.	Baseline to documented progressive disease (Approximately 15 Months)
Primary	Safety and tolerability of IMU-201 graded per terminology criteria for adverse events (CTCAE) version 5.00 (Dose Escalation)	Safety and Tolerability Measures include: Frequency of adverse events (AEs) graded per terminology criteria for adverse events (CTCAE) version 5.00.	Baseline to Day 29
Primary	Identify Optimal Biological Dose (OBD) with safety/tolerability graded per terminology criteria for adverse events (CTCAE) version 5.00 and Immuogenicity (Dose Escalation).	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.	Baseline to Day 43
Primary	Overall response rate (ORR) (Dose Expansion)	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.	Baseline to documented progressive disease (Approximately 15 months)
Secondary	Overall response rate (ORR) (Dose Escalation)	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.	Baseline to documented progressive disease (Approximately 15 Months)
Secondary	Progression free survival (PFS) (Dose Escalation/Expansion)	Efficacy of IMU-201 will be evaluated by progression free survival at OBD of IMU-201.	Baseline to documented progressive disease or death due to any cause (Approximately 15 Months)
Secondary	Overall survival (OS) (Dose Escalation/Expansion)	Efficacy of IMU-201 will be evaluated by overall survival at OBD of IMU-201.	Baseline to death from any cause (Approximately 15 Months)
Secondary	Duration of response (DOR) (Dose Escalation/Expansion)	Efficacy of IMU-201 will be evaluated by duration of response at OBD of IMU-201.	From date of earliest CR or PR until the date of first documented progression or death from any cause (Approximately 15 Months)

External Links

•   Imugene Limited