Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04432207
Recruitment Status : Recruiting
First Posted : June 16, 2020
Last Update Posted : August 17, 2021
Sponsor:
Information provided by (Responsible Party):
Imugene Limited

Brief Summary:
The phase 1 study is an open label, multi-center, non-randomized, dose escalation and expansion study designed to assess the safety, tolerability, and immunogenicity of IMU-201(PD1-Vaxx) as monotherapy in patients with PD-L1 expressing non-small cell lung cancer (NSCLC).

Condition or disease Intervention/treatment Phase
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 Drug: IMU-201 (administered as PD1-Vaxx) Phase 1

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 study is designed to assess the safety, tolerability, and immunogenicity of IMU-201 (PD1-Vaxx) as monotherapy in patients with PD-L1 expressing non-small cell lung cancer (NSCLC). The monotherapy dose-escalation of IMU-201 (PD1-Vaxx) will establish the optimal biological dose. Once established, the dose cohort will be expanded to a total of 10 participants. Once the monotherapy optimal biological dose is established and expansion complete, the protocol will be modified to include a combination dose escalation with standard of care treatment.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Multi-Center, Dose Escalation/Expansion, Phase 1 Study of IMU-201 (PD1-Vaxx), a B-Cell Immunotherapy, in Adults With Non-Small Cell Lung Cancer
Actual Study Start Date : November 30, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose Escalation: Monotherapy Cohort 1
10 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection
Drug: IMU-201 (administered as PD1-Vaxx)
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, and 29, and then on Day 64 and every subsequent 63 days until discontinuation from study.
Other Names:
  • PD1-Vaxx
  • APi2568

Experimental: Dose Escalation: Monotherapy Cohort 2
50 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection
Drug: IMU-201 (administered as PD1-Vaxx)
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, and 29, and then on Day 64 and every subsequent 63 days until discontinuation from study.
Other Names:
  • PD1-Vaxx
  • APi2568

Experimental: Dose Escalation: Monotherapy Cohort 3
100 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection
Drug: IMU-201 (administered as PD1-Vaxx)
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, and 29, and then on Day 64 and every subsequent 63 days until discontinuation from study.
Other Names:
  • PD1-Vaxx
  • APi2568




Primary Outcome Measures :
  1. Safety and tolerability of IMU-201 as monotherapy graded per terminology criteria for adverse events (CTCAE) version 5.00 [ Time Frame: 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.

  2. Identify Optimal Biological Dose (OBD) with safety/tolerability graded per terminology criteria for adverse events (CTCAE) version 5.00 and Immuogenicity. [ Time Frame: 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 :
  1. Overall response rate (ORR) [ Time Frame: Baseline to documented progressive disease (Approximately 15 Months) ]
    Efficacy of IMU-201 as monotherapy 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.

  2. Progression free survival (PFS) [ Time Frame: Baseline to documented progressive disease or death due to any cause (Approximately 15 Months) ]
    Efficacy of IMU-201 as monotherapy will be evaluated by progression free survival at OBD of IMU-201.

  3. Overall survival (OS) [ Time Frame: Baseline to death from any cause (Approximately 15 Months) ]
    Efficacy of IMU-201 as monotherapy will be evaluated by overall survival at OBD of IMU-201


Other Outcome Measures:
  1. Exploratory Outcome: Humoral immunogenicity of IMU-201 [ Time Frame: Baseline to documented progressive disease (Approximately 15 Months) ]
    Humoral immunogenicity evaluated by PD-1 specific antibodies (IgG, IgM).

  2. Exploratory Outcome: Cellular immunogenicity of IMU-201 [ Time Frame: Baseline to documented progressive disease (Approximately 15 Months) ]
    Cellular immunogenicity evaluated by vaccine-specific cytokine levels as well as analysis of regulatory and effector T and B cells.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Informed of the investigational nature of this study and has given written informed consent in accordance with institutional, local, and national guidelines;
  2. Histologically confirmed non-small-cell lung cancer (NSCLC) tumor stage IIIb or IV (3 major types of NSCLC are acceptable including squamous, adenocarcinoma, and large cell carcinoma);
  3. Progressed on an approved PD-1 inhibitor or an approved PD-L1 inhibitor. Patients previously treated with a combination of an approved PD-1 or an approved anti-PD-L1 inhibitor and chemotherapy may be included with agreement of Imugene Limited;
  4. Age of at least 18 years;
  5. Life expectancy of at least 12 weeks in the opinion of the Investigator;
  6. Tumor PD-L1 overexpression with Tumor Proportion Score (TPS) ≥ 50%. Participants with PD-L1 TPS ≥ 1% expression may be included with agreement of Imugene Limited;
  7. Zubrod/ECOG score performance status 0-1;
  8. At least one measurable lesion as defined by RECIST 1.1 criteria. Patients with non-measurable lesions may be included with agreement of Imugene Limited;
  9. Adequate hematologic function: Absolute neutrophil count (ANC) > 1.5x109/L, platelet count at > 100x109/L, and hemoglobin > 9 g/dL;
  10. Adequate liver function evidenced by bilirubin at < 1.5x laboratory upper limit of normal [ULN], and ALT and AST at < 3x laboratory ULN if no liver involvement or ALT and AST at < 5x laboratory ULN with liver involvement;
  11. Adequate renal function (creatinine at < 1.5x laboratory ULN);
  12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
  13. Male participants must agree to use a highly effective method of contraception throughout the study and for at least 180 days after the last dose of assigned treatment;
  14. If female, must be at least 2 years post-menopausal (defined as post-menopausal with at least 24 consecutive months without menstruation) or documented surgically sterile.

Exclusion Criteria:

  1. Prior therapy for advanced NSCLC within 6 weeks prior to Day 1;
  2. Continuous systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 4 weeks prior to first dose of study treatment. Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalents are permitted in the absence of active auto-immune disease;
  3. Any previous grade 3 or higher toxicity to a PD-1 inhibitor or PD-L1 inhibitor;
  4. Known brain metastases requiring steroid treatment, or signs and symptoms indicating suspected brain metastases;
  5. Current or previous history of auto-immune disease;
  6. NSCLC expressing epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), B-Raf proto-oncogene (BRAF) or ROS proto-oncogene 1 (ROS1) mutations;
  7. Prior organ transplant;
  8. Concurrent active malignancy except for adequately controlled limited basal cell carcinoma of the skin;
  9. 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;
  10. Active infection requiring intravenous antibiotics;
  11. Positive for human immunodeficiency virus (HIV) (HIV 1/2 antibodies) or active hepatitis B (HBsAg reactive) or active hepatitis C (HCV ribonucleic acid [RNA] qualitative) infection;
  12. Major surgery within 4 weeks prior to study entry. Minor surgery (excluding diagnostic biopsy) within 1 week prior to study entry;
  13. Has received a live-virus vaccination within 4 weeks of first dose of IMU-201. Seasonal flu vaccines that do not contain live virus are permitted;
  14. Current or recent (within 6 weeks of first IMU-201 dose) treatment with another investigational drug or participation in another investigational study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04432207


Contacts
Layout table for location contacts
Contact: Anthony J Good, PhD 03 9824 5254 anthony.good@imugene.com
Contact: Bonnie Nixon, BS bnixon@imugene.com

Locations
Layout table for location information
United States, Arizona
Mayo Clinic Recruiting
Phoenix, Arizona, United States, 85054
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
United States, Ohio
Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Australia, New South Wales
Chris O'Brien Lifehouse Recruiting
Camperdown, New South Wales, Australia, 2050
Macquarie University Recruiting
Macquarie, New South Wales, Australia, 2109
Australia, Victoria
Cabrini Malvern Hospital Recruiting
Melbourne, Victoria, Australia, 3000
Sponsors and Collaborators
Imugene Limited
Additional Information:
Layout table for additonal information
Responsible Party: Imugene Limited
ClinicalTrials.gov Identifier: NCT04432207    
Other Study ID Numbers: IMU.201.101
First Posted: June 16, 2020    Key Record Dates
Last Update Posted: August 17, 2021
Last Verified: August 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Large Cell
Adenocarcinoma of Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type