Clinical Trials /

Study of Adagloxad Simolenin (OBI-822)/OBI-821 in the Adjuvant Treatment of Patients With Globo H Positive TNBC

NCT03562637

Description:

The GLORIA study is a Phase III, randomized, open-label study to prospectively evaluate the efficacy and safety of adagloxad simolenin (OBI 822)/OBI-821 in the adjuvant treatment of patients with high risk, early stage Globo-H Positive TNBC.

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Adagloxad Simolenin (OBI-822)/OBI-821 in the Adjuvant Treatment of Patients With Globo H Positive TNBC
  • Official Title: The GLORIA Study: A Phase 3, Randomized, Open-Label Study of the Anti-Globo H Vaccine Adagloxad Simolenin (OBI-822)/OBI-821 in the Adjuvant Treatment of Patients With High Risk, Early Stage Globo H-Positive Triple Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: OBI-822-011
  • NCT ID: NCT03562637

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
adagloxad simolenin combined with OBI-821Adagloxad simolenin + OBI-821 in conjunction with SOC

Purpose

The GLORIA study is a Phase III, randomized, open-label study to prospectively evaluate the efficacy and safety of adagloxad simolenin (OBI 822)/OBI-821 in the adjuvant treatment of patients with high risk, early stage Globo-H Positive TNBC.

Trial Arms

NameTypeDescriptionInterventions
Adagloxad simolenin + OBI-821 in conjunction with SOCExperimentalParticipants will be administered adagloxad simolenin combined with OBI-821 for up to a total of 21 subcutaneous injections over a period of 100 weeks. Patient will also receive standard of care (SOC) treatment.
  • adagloxad simolenin combined with OBI-821
Standard of Care treatmentActive ComparatorStudy visit intervals will be identical to those in Arm 1. Patient will receive standard of care (SOC) treatment.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Documented radiographic and histopathologic confirmed primary localized invasive
                 breast cancer.
    
              -  Histologically documented TNBC (estrogen receptor negative [ER-]/progesterone receptor
                 negative [PR-]/human epidermal growth factor 2 negative [HER2-]) defined as
                 ER-negative and PR-negative (≤5% positive cells stain by IHC for both ER and PR), and
                 negative HER2/neu- status, confirmed on tumor sample.
    
              -  HER2/neu negative will be defined as one of the following criteria:
    
                   -  IHC 0 or 1+
    
                   -  Single-probe average HER2 gene copy number of <6 signals/nucleus
    
                   -  Dual-probe fluorescent in-situ hybridization (FISH) HER2/neu chromosome 17
                      (CEP17) non-amplified ratio of <2
    
              -  Globo H IHC H-score ≥15 from the residual primary site/or lymph node (if primary site
                 is not available) tumor obtained at time of definitive surgery. Globo H expression
                 will be determined during pre-screening by Central lab. Instructions for submission of
                 slides/tumor tissue blocks are provided in the protocol and study Lab Manual.
    
              -  No evidence of metastatic disease in chest, abdomen and pelvis by CT or other adequate
                 imagining during the Screening Phase. Imaging within 3 months prior to randomization
                 is acceptable as baseline scan. Bone scans and imaging of the brain at screening is
                 optional, and should be symptom directed.
    
              -  High risk patients with no evidence of disease after completing standard treatment and
                 meeting ONE of the following criteria:
    
                   -  Neoadjuvant chemotherapy followed by definitive surgery: Residual invasive
                      disease following neoadjuvant chemotherapy defined as: A contiguous focus of
                      residual invasive cancer in the surgical breast measuring ≥1 cm in diameter
                      and/or with residual invasive cancer in at least one axillary node
                      (micrometastases or macrometastases), as determined by local pathology review.
    
                   -  Definitive surgery followed by adjuvant chemotherapy: Pathological Stage IIB,
                      Stage IIIA , Stage IIIB, or Stage IIIC disease according to the 8th edition of
                      the American Joint Committee on Cancer (AJCC) Cancer Staging Manual.
    
              -  Must have completed a standard taxane, and/or anthracycline-based multi-agent
                 chemotherapy regimen either in the neoadjuvant or adjuvant setting (e.g., National
                 Comprehensive Cancer Network recommended regimens):.
    
                   -  At least 4 cycles of a standard multi-agent chemotherapy regimen must have been
                      received, unless precluded by toxicities
    
                   -  Post operative adjuvant capecitabine or a platinum monotherapy in patients with
                      residual disease after neoadjuvant chemotherapy is allowed.
    
              -  Randomization must occur within 12 weeks after completion of standard of care
                 treatment (surgery and/or chemotherapy) and within 46 weeks from the date of
                 definitive surgery. Note: patients receiving adjuvant capecitabine or platinum
                 monotherapy after neoadjuvant multi-agent chemotherapy may be randomized and initiate
                 study treatment during (or within 12 weeks after completion of) the adjuvant
                 capecitabine or platinum monotherapy.
    
              -  All treatment-related toxicities resolved to Grade <1 on National cancer institute
                 Common Terminology Criteria for Adverse Events (NCI-CTCAE version 5.0) criteria
                 (except hair loss and ≤Grade 2 neuropathy, which are acceptable).
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
    
              -  Females must be either of non-childbearing potential, i.e., surgically sterilized
                 (have documented sterilization, bilateral oophorectomy/salpingectomy at least 3 months
                 before the start of the trial and/or hysterectomy), or one year postmenopausal; or if
                 of childbearing potential must have a negative pregnancy test (urine or serum) at
                 randomization.
    
              -  Males and females of childbearing potential and their partners must be willing to use
                 effective contraception during the entire Treatment Phase period and for at least 4
                 weeks (28 days) after the last dose of study treatment.
    
              -  Adequate hematological, hepatic and renal function as defined below:
    
                   -  Absolute neutrophil count (ANC) ≥1,500/µL
    
                   -  Platelets ≥75,000/µL
    
                   -  Hemoglobin ≥8.5g/dL
    
                   -  Serum creatinine ≤1.5 × upper limit of normal (ULN) or calculated creatinine
                      clearance ≥55 mL/min for subjects with creatinine levels >1.5 × institutional ULN
                      (glomerular filtration rate can also be used in place of creatinine or creatinine
                      clearance may be calculated per institutional standard)
    
                   -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN
    
                   -  Alkaline Phosphatase (ALP) ≤2.5 × ULN
    
                   -  Serum total bilirubin ≤1.5 × ULN (unless Gilbert's disease is documented)
    
              -  Consent to participate with a signed and dated Institutional Review Board
                 (IRB)/Independent Ethics Committee (IEC) approved patient informed consent for the
                 study prior to beginning any specific study procedures.
    
              -  Ability to understand and willingness to complete all protocol required procedures.
    
            Exclusion Criteria:
    
              -  Local recurrence of or previous history of ipsilateral or contralateral invasive
                 breast cancer within 10 years prior to randomization.
    
              -  Definitive clinical or radiologic evidence of metastatic disease
    
              -  Synchronous bilateral breast cancer, unless both tumors are confirmed as TNBC.
    
              -  Have received any post-operative immunotherapy with antigen, antibody, immune
                 checkpoint inhibitors (Programmed cell death-1 [PD-1]/ Programmed cell
                 death-ligand-1inhibitors [PD-L-1], anti-cytotoxic T lymphocyte associated protein 4
                 [CTLA 4] therapy), or other anti-cancer vaccines (neoadjuvant receipt of immune
                 checkpoint inhibitors will not be exclusionary if the patient meets all other
                 eligibility criteria).
    
              -  Concomitant treatment with approved anticancer therapy or immunotherapy including
                 checkpoint inhibitors (e.g. PD-1 inhibitors) or other investigational therapy, if
                 expected during the study. Adjuvant capecitabine or platinum monotherapy is allowed
                 during the study.
    
              -  A history of other malignancies (except non melanoma skin carcinoma, carcinoma in situ
                 of the uterine cervix, follicular or papillary thyroid cancer) within 5 years prior to
                 randomization.
    
              -  Have any active autoimmune disease or disorder that requires systemic
                 immunosuppressive/immunomodulatory therapy. NOTE: Autoimmune diseases that are
                 confined to the skin (e.g., psoriasis) that can be treated with topical steroids alone
                 are allowed during the study.
    
              -  Oral/parenteral corticosteroid treatment (>5 mg/day of prednisone/equivalent), within
                 2 weeks prior to randomization or anytime during the study. NOTE: inhaled steroids for
                 treatment of asthma; and topical steroids are allowed during the study.
    
              -  Any known uncontrolled concurrent illness that would limit compliance with study
                 requirements, including but not limited to ongoing or active infections, symptomatic
                 congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric
                 disorders, or substance abuse.
    
              -  Any known hypersensitivity to active/inactive ingredients in the study drug
                 formulation or known severe allergy or anaphylaxis to fusion proteins.
    
              -  Prior receipt of a glycoconjugate vaccine for cancer immunotherapy.
    
              -  Known history or positive for human immunodeficiency virus (HIV positive), unless on
                 effective anti-retroviral therapy with undetectable viral load within 6 months of
                 therapy (note: HIV testing not required for study entry).
    
              -  Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection prior to
                 randomization. Patients who have completed curative therapy for HCV are eligible. For
                 patients with evidence of chronic HBV infection, the HBV viral load must be
                 undetectable on suppressive therapy. (note: HBV/HCV testing is not required for study
                 entry).
    
              -  Any condition, including significant diseases and/or laboratory abnormalities that
                 would place the patient at unacceptable risk for study participation.
    
              -  Currently pregnant or breastfeeding women.
    
              -  Currently participating in or has participated in a breast cancer therapeutic clinical
                 trial within 4 weeks (24 days) prior to randomization.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Measuring the effect of adagloxad simolenin (OBI-822)/OBI-821 treatment on improving invasive disease free survival (IDFS) in the study population.
    Time Frame:5 years
    Safety Issue:
    Description:The outcome measure of the study is IDFS, defined by the STEEP system as the first occurrence of the time from the date of randomization to the date of first invasive disease recurrence (local, regional or distant), the date of secondary primary invasive cancer (breast or not), or the date of death from any cause.

    Secondary Outcome Measures

    Measure:Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Overall Survival (OS).
    Time Frame:7 years
    Safety Issue:
    Description:OS is defined as the time from randomization to date of death from any cause
    Measure:Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Quality of Life (QoL).
    Time Frame:7 years
    Safety Issue:
    Description:QoL defined as time to definitive deterioration in Health-related Quality of Life (HRQOL) using the global health status/QoL scale from European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and the European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L). QoL baseline established at randomization. Definitive deterioration defined as a 5% worsening relative to baseline in the HRQOL scale score from EORTC QLQ-C30 questionnaires with no subsequent improvement above threshold, scored with the EORTC QLQ-C30 v3.0 Scoring Manual. The EQ-5D-5L questionnaire assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, rated by the patient. It is a standardized measure of health status to provide a simple, generic measure of health for clinical and economic appraisal. 28 questions have a 4 point scale: not at all(1) to very much(4). 2 questions have a 7-point scale: very poor (1) to excellent(7).
    Measure:Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Breast cancer-free interval (BCFI).
    Time Frame:7 years
    Safety Issue:
    Description:BCFI is defined by the STEEP system as the first occurrence of the time from the date of randomization to the date of the first invasive disease recurrence (local, regional or distant), the date of ductal carcinoma in situ (ipsilateral or contralateral), or the date of death from breast cancer
    Measure:Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Distant disease-free survival (DDFS).
    Time Frame:7 years
    Safety Issue:
    Description:DDFS is defined by the STEEP system as the first occurrence of the time from the date of randomization to the date of the first distant disease recurrence, the date of the second primary invasive cancer (non-breast), or the date of death from any cause
    Measure:Incidence and severity of adverse events (AEs) [Time Frame: AEs will be noted as it occurs, with a timeframe from beginning of randomization to 4 weeks after last dose of study treatment.]
    Time Frame:2 years
    Safety Issue:
    Description:Adverse Events will be graded and recorded by investigators per National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0).

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:OBI Pharma, Inc

    Trial Keywords

    • Neoadjuvant chemotherapy
    • Adjuvant chemotherapy
    • TNBC

    Last Updated

    March 5, 2021