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

NCT ID: NCT04432207

Last Updated: 2024-11-07

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-30
• Study Completion Date: 2025-05-31

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.

Conditions

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; Large Cell Carcinoma Lung; Adenocarcinoma Lung

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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%

Group Type: EXPERIMENTAL

IMU-201 (administered as PD1-Vaxx) - Regimen 2

Intervention Type: BIOLOGICAL

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.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered every 2 weeks (Q2W) starting Day 15 until discontinuation from study.

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%

Group Type: EXPERIMENTAL

IMU-201 (administered as PD1-Vaxx) - Regimen 2

Intervention Type: BIOLOGICAL

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.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered every 2 weeks (Q2W) starting Day 15 until discontinuation from study.

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%

Group Type: EXPERIMENTAL

IMU-201 (administered as PD1-Vaxx) - Regimen 2

Intervention Type: BIOLOGICAL

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.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered every 2 weeks (Q2W) starting Day 15 until discontinuation from study.

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

Group Type: EXPERIMENTAL

IMU-201 (administered as PD1-Vaxx) - Regimen 3

Intervention Type: BIOLOGICAL

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.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered every 2 weeks (Q2W) starting Day 15 until discontinuation from study.

Standard of care chemotherapy

Intervention Type: DRUG

Chemotherapy to be administered according to the prescribing information.

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

Group Type: EXPERIMENTAL

IMU-201 (administered as PD1-Vaxx) - Regimen 3

Intervention Type: BIOLOGICAL

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.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered every 2 weeks (Q2W) starting Day 15 until discontinuation from study.

Standard of care chemotherapy

Intervention Type: DRUG

Chemotherapy to be administered according to the prescribing information.

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

Group Type: EXPERIMENTAL

IMU-201 (administered as PD1-Vaxx) - Regimen 3

Intervention Type: BIOLOGICAL

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.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered every 2 weeks (Q2W) starting Day 15 until discontinuation from study.

Standard of care chemotherapy

Intervention Type: DRUG

Chemotherapy to be administered according to the prescribing information.

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%

Group Type: EXPERIMENTAL

IMU-201 (administered as PD1-Vaxx) - Regimen 2

Intervention Type: BIOLOGICAL

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.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered every 2 weeks (Q2W) starting Day 15 until discontinuation from study.

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%

Group Type: EXPERIMENTAL

IMU-201 (administered as PD1-Vaxx) - Regimen 2

Intervention Type: BIOLOGICAL

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.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered every 2 weeks (Q2W) starting Day 15 until discontinuation from study.

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

Group Type: EXPERIMENTAL

IMU-201 (administered as PD1-Vaxx) - Regimen 3

Intervention Type: BIOLOGICAL

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.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered every 2 weeks (Q2W) starting Day 15 until discontinuation from study.

Standard of care chemotherapy

Intervention Type: DRUG

Chemotherapy to be administered according to the prescribing information.

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%

Group Type: EXPERIMENTAL

IMU-201 (administered as PD1-Vaxx) - Regimen 1

Intervention Type: BIOLOGICAL

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.

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%

Group Type: EXPERIMENTAL

IMU-201 (administered as PD1-Vaxx) - Regimen 1

Intervention Type: BIOLOGICAL

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.

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%

Group Type: EXPERIMENTAL

IMU-201 (administered as PD1-Vaxx) - Regimen 1

Intervention Type: BIOLOGICAL

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.

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%

Group Type: EXPERIMENTAL

IMU-201 (administered as PD1-Vaxx) - Regimen 1

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

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.

Intervention Type: BIOLOGICAL

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.

Intervention Type: BIOLOGICAL

Atezolizumab

Atezolizumab will be administered every 2 weeks (Q2W) starting Day 15 until discontinuation from study.

Intervention Type: DRUG

Standard of care chemotherapy

Chemotherapy to be administered according to the prescribing information.

Intervention Type: DRUG

Other Intervention Names

PD1-Vaxx; APi2568; PD1-Vaxx; APi2568; PD1-Vaxx; APi2568; TECENTRIQ

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Imugene Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Mayo Clinic

Phoenix, Arizona, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Ohio State University Medical Center

Columbus, Ohio, United States

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Macquarie University

Macquarie, New South Wales, Australia

Cabrini Malvern Hospital

Melbourne, Victoria, Australia

Countries

United States; Australia

Related Links

https://www.imugene.com/

Imugene Limited

Other Identifiers

IMU.201.101

Identifier Type: -

Identifier Source: org_study_id