Clinical Trials /

A Study of IMU-131(HER-Vaxx) and Chemotherapy Compared to Chemotherapy Only in Patients With HER2 Positive Advanced Gastric Cancer

NCT02795988

Description:

The Phase 1b study is an open-label, multicenter dose escalation study designed to assess the safety, tolerability, immunogenicity and recommended phase 2 dose (RP2D) of IMU-131. The RP2D will be evaluated in the dose expansion Phase 2 study. The Phase 2 study is a randomized, open label comparison of IMU-131 plus standard of care chemotherapy versus standard of care chemotherapy alone.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of IMU-131(HER-Vaxx) and Chemotherapy Compared to Chemotherapy Only in Patients With HER2 Positive Advanced Gastric Cancer
  • Official Title: A Phase 1b/2 Open-Label Study With Randomization in Phase 2 of IMU-131 HER2/Neu Peptide Vaccine Plus Standard of Care Chemotherapy in Patients With HER2/Neu Overexpressing Metastatic or Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction

Clinical Trial IDs

  • ORG STUDY ID: IMU.ACS.001
  • NCT ID: NCT02795988

Conditions

  • Gastrointestinal Neoplasms
  • Adenocarcinoma

Interventions

DrugSynonymsArms
IMU-131HER-VaxxPhase 1b
Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.Standard of Care ChemotherapyPhase 1b

Purpose

The Phase 1b study is an open-label, multicenter dose escalation study designed to assess the safety, tolerability, immunogenicity and recommended phase 2 dose (RP2D) of IMU-131. The RP2D will be evaluated in the dose expansion Phase 2 study. The Phase 2 study is a randomized, open label comparison of IMU-131 plus standard of care chemotherapy versus standard of care chemotherapy alone.

Detailed Description

      IMU-131 is a single peptide structure composed of 3 individual B-cell epitope peptide
      sequences selected from HER2/neu structure. Polyclonal antibodies against IMU-131 peptides
      bind three separate regions of the HER2 receptor and also to the dimerization loop of the
      HER2 receptor, preventing dimerization, which in turn inhibits intracellular signaling. This
      blockade of the HER2 signaling pathways is thought to be substantially greater than that with
      trastuzumab alone. Safety and immunogenicity of the 3 peptides have been shown in Phase 1a
      testing of an earlier formulation of IMU-131. The shelf stability of the Phase 1a vaccine was
      not optimal and hence the formulation was adjusted for IMU-131. The three B-cell epitope
      peptides (P4, P6 and P7) were combined in a specific order resulting in a single fusion
      peptide of 49 amino acids in length (P467). This new formulation of IMU-131 has extended
      stability and improved immunogenicity compared to the formulation used previously. The new
      vaccine IMU-131 produces a stronger and more rapid polyclonal antibody response and is
      efficient to manufacture compared with previous formulations. Based on these three known
      epitopes (P4, P6 and P7), the investigators developed a single peptide antigen (P467), which
      allows simplification of the manufacturing process.

      It is hypothesized that administration of IMU-131 in addition to chemotherapy will prolong
      survival and may delay tumor progression and/or reduce tumor burden in patients with HER2/neu
      overexpressing gastric or gastroesophageal junction (GEJ) adenocarcinoma (otherwise known as
      Advanced Cancer of the Stomach (ASC)).

      The Phase 1b study aims to determine the safety and tolerability of IMU-131 and identify the
      Recommended Phase 2 Dose (RP2D) of IMU-131 in combination with chemotherapy in HER2/neu
      overexpressing ACS to carry into the Phase 2 dose expansion study. The Phase 2 component will
      be submitted as an amendment and will be initiated following completion of Phase 1b. Phase 2
      will be designed to further characterize the safety and to explore clinical activity of
      IMU-131 in combination with chemotherapy in HER2/neu overexpressing ACS.The Phase 2 study is
      a randomized, open label comparison of IMU-131 plus standard of care chemotherapy versus
      standard of care chemotherapy alone.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1bExperimental10, 30, 50μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine
  • IMU-131
  • Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.
Phase 2 - IMU 131 plus chemotherapyExperimental50 μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and Capecitabine.
  • IMU-131
  • Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.
Phase 2 - Chemotherapy onlyExperimentalCisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and Capecitabine.
  • Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.

Eligibility Criteria

        Inclusion Criteria:

          1. Patient has been informed of the investigational nature of this study and has given
             written informed consent in accordance with institutional, local, and national
             guidelines;

          2. Age ≥ 20 years old;

          3. Life expectancy of at least 12 weeks;

          4. Phase 1b: No prior chemotherapy or radiotherapy for advanced gastric or GEJ cancer
             within 6 months prior to Day 0; Phase 2: No prior chemotherapy or radiotherapy for
             advanced gastric or GEJ cancer within 3 months prior to Day 0;

          5. Metastatic gastric or GEJ adenocarcinoma, or locally advanced disease not amenable to
             surgical resection;

          6. HER2/neu overexpression (3+ by immunohistochemistry (IHC) or if IHC 2+ confirmed by
             fluorescent in situ hybridization [FISH] or chromogenic in situ hybridization [CISH]).
             Patients with IHC 2+ expression without confirmation of overexpression by fluorescent
             in situ hybridization [FISH] or chromogenic in situ hybridization [CISH]) may be
             included in Phase 1b with agreement of Imugene Limited;

          7. Phase 1b: ECOG performance status 0-1; Phase 2: ECOG performance status 0-2;

          8. At least one measurable lesion as defined by RECIST 1.1 criteria. Patients with
             non-measurable lesions may be included in Phase1b with agreement of Imugene Limited;

          9. Adequate left ventricular ejection function at baseline, defined as LVEF > 50% by
             echocardiogram or MUGA scan (Multi Gated Acquisition Scan);

         10. Adequate hematologic function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet
             count ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL;

         11. Adequate liver function evidenced by bilirubin ≤ 1.5 x laboratory upper limit of
             normal [ULN], and ALT and AST ≤ 3 x laboratory ULN if no liver involvement or ALT and
             AST ≤ 5 times laboratory ULN with liver involvement;

         12. Adequate renal function (creatinine ≤ 1.5 x laboratory ULN);

         13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
             and other study procedures.

         14. Male and female patients of childbearing potential must agree to use a highly
             effective method of contraception throughout the study and for at least 28 days after
             the last dose of assigned treatment (see section 4.3 for details). A patient is of
             childbearing potential if, in the opinion of the investigator, he/she is biologically
             capable of having children and is sexually active.

        Exclusion Criteria:

          1. Previous treatment with trastuzumab or any other HER2/neu targeting antibody or agent;

          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. Prior organ transplant;

          4. Phase 1b: Patient not considered a candidate for 5-FU, capecitabine, or cisplatin
             chemotherapy; Phase 2: Patient not considered a candidate for 5-FU, capecitabine,
             cisplatin or oxaliplatin chemotherapy;

          5. History of documented congestive heart failure; angina pectoris requiring antianginal
             medication; evidence of transmural infarction on ECG; poorly controlled hypertension;
             clinically significant valvular heart disease; high risk uncontrolled arrhythmias; or
             New York Heart Association (NYHA) class II heart disease;

          6. If on warfarin (Coumadin®) or other vitamin K antagonists;

          7. Concurrent active malignancy except for adequately controlled limited basal cell
             carcinoma of the skin;

          8. Peripheral neuropathy or hearing loss of NCI CTCAE Grade > 2;

          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 IV 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. Pregnant or lactating females;

         13. Major surgery within 4 weeks prior to study entry. Minor surgery (excluding diagnostic
             biopsy) within 1 week prior to study entry;

         14. Has received a live-virus vaccination within 4 weeks of first study vaccination.
             Seasonal flu vaccines that do not contain live virus are permitted;

         15. Current or recent (within 4 weeks of first IMU-131 vaccination) treatment with another
             investigational drug or participation in another investigational study.

         16. Phase 2: Patients with a known diphtheria toxoid hypersensitivity.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of IMU-131 (Phase 1b)
Time Frame:Day 0 to Day 56
Safety Issue:
Description:The safety and tolerability of IMU-131 will be evaluated by adverse events (AEs) and laboratory measurements.

Secondary Outcome Measures

Measure:Progression Free Survival (Phase 2)
Time Frame:Day 0 to Progression (approx. 7.5 months)
Safety Issue:
Description:To evaluate other efficacy measures of IMU-131: progression-free survival (PFS).
Measure:Time to progression (Phase 2)
Time Frame:Day 0 to Progression (approx. 7.5 months)
Safety Issue:
Description:To evaluate other efficacy measures of IMU-131: time to progression (TTP).
Measure:Disease Control Rate (Phase 2)
Time Frame:Day 0 to Progression (approx. 7.5 months)
Safety Issue:
Description:To evaluate other efficacy measures of IMU-131: disease control rate (DCR).
Measure:Objective Response Rate (Phase 2)
Time Frame:Day 0 to Progression (approx. 7.5 months)
Safety Issue:
Description:To evaluate other efficacy measures of IMU-131: objective response rate (ORR).
Measure:Duration of Objective Response (Phase 2)
Time Frame:Day 0 to Progression (approx. 7.5 months)
Safety Issue:
Description:To evaluate other efficacy measures of IMU-131: duration of objective response (DOR).
Measure:Change in Tumor Size (Phase 2)
Time Frame:Day 0 to Progression (approx. 7.5 months)
Safety Issue:
Description:To evaluate other efficacy measures of IMU-131: change in tumor size (CTS).
Measure:Humoral and cellular immunogenicity of IMU-131(Phase 2)
Time Frame:Day 0 to Progression (approx. 7.5 months)
Safety Issue:
Description:Values and changes from randomization in humoral and cellular immunogenicity data including P467-specific antibodies (IgG), Her-2-specific antibodies (IgG), vaccine-specific cytokine levels and regulatory and effector T and B cells.
Measure:Incidence of TEAE's (Phase 2)
Time Frame:Day 0 to Progression (approx. 7.5 months)
Safety Issue:
Description:Safety will be assessed by comparing the incidence of TEAE's & SAE's in each group.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Imugene Limited

Trial Keywords

  • Secondary

Last Updated

May 4, 2020