Clinical Trials /

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

NCT04432207

Description:

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 and in combination with Standard of Care (SOC) treatment in participants with PD-L1 expressing non-small cell lung cancer (NSCLC).

Related Conditions:
  • Large Cell Lung Carcinoma
  • Lung Adenocarcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: IMU.201.101
  • NCT ID: NCT04432207

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

Interventions

DrugSynonymsArms
IMU-201 (administered as PD1-Vaxx)PD1-Vaxx, APi2568Dose Escalation: Combination
Standard of care treatment for NSCLCDose Escalation: Combination

Purpose

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 and in combination with Standard of Care (SOC) treatment in participants with PD-L1 expressing non-small cell lung cancer (NSCLC).

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 and in combination with Standard of Care (SOC) treatment in
      participants with PD-L1 expressing non-small cell lung cancer (NSCLC). The study consists of
      two parts. Part 1, monotherapy dose-escalation of IMU-201 (PD1-Vaxx) to establish an optimal
      biological dose as monotherapy (Part 1a) followed by a combination dose escalation with
      standard of care treatment to establish a combination optimal biological dose of IMU-201
      (PD1-Vaxx)(Part 1b). Part 2 dose expansion, will further characterize the safety,
      tolerability, and immunogenicity of IMU-201 in combination with SOC treatment for NSCLC at
      the defined expansion dose-level from Part 1b.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation: Monotherapy Cohort 1Experimental10 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection
  • IMU-201 (administered as PD1-Vaxx)
Dose Escalation: Monotherapy Cohort 2Experimental50 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection
  • IMU-201 (administered as PD1-Vaxx)
Dose Escalation: Monotherapy Cohort 3Experimental100 μg/dose IMU-201 as a 0.5 mL PD1-Vaxx injection
  • IMU-201 (administered as PD1-Vaxx)
Dose Escalation: CombinationExperimentalIn Part 1b combination dose escalation, participants receive MU-201 in combination with SOC treatment for NSCLC with the first dose cohort starting at one dose level below the monotherapy optimal biological dose (mOBD-1) established in part 1a monotherapy dose escalation.
  • IMU-201 (administered as PD1-Vaxx)
  • Standard of care treatment for NSCLC
Dose Expansion: CombinationExperimentalIn Part 2 dose expansion, participants will receive IMU-201 in combination with SOC treatment for NSCLC at the combination optimal biological dose determined in Part 1b combination dose escalation.
  • IMU-201 (administered as PD1-Vaxx)
  • Standard of care treatment for NSCLC

Eligibility 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. Part 1a, monotherapy dose escalation: Progressed on ICI or an ICI and chemotherapy;
             Part 1b and 2, combination dose escalation and expansion: No previous treatment with
             an ICI;

          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 in Part 1a
             only;

          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. Part 1a, monotherapy dose escalation: Prior therapy for advanced NSCLC within 6 weeks
             prior to Day 1; Part 1b and Part 2, combination dose escalation and expansion: Prior
             treatment with an ICI;

          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 an ICI;

          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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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 Issue:
Description:Safety and Tolerability Measures include: Adverse events (AEs); dose-limiting toxicities (DLTs) graded per terminology criteria for adverse events (CTCAE) version 5.00.

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Baseline to documented progressive disease (Approximately 15 Months)
Safety Issue:
Description:Efficacy of IMU-201 as monotherapy and in combination with standard of care 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.
Measure:Progression free survival (PFS)
Time Frame:Baseline to documented progressive disease or death due to any cause (Approximately 15 Months)
Safety Issue:
Description:Efficacy of IMU-201 as monotherapy and in combination with standard of care will be evaluated by progression free survival at OBD of IMU-201.
Measure:Overall survival (OS)
Time Frame:Baseline to death from any cause (Approximately 15 Months)
Safety Issue:
Description:Efficacy of IMU-201 as monotherapy and in combination with standard of care will be evaluated by overall survival at OBD of IMU-201

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Imugene Limited

Last Updated

August 10, 2020