Clinical Trials /

Study of Glembatumumab Vedotin in gpNMB-Expressing, Advanced or Metastatic SCC of the Lung

NCT02713828

Description:

Patients with advanced or metastatic, gpNMB-expressing Squamous Cell Carcinoma (SCC) of the lung who have failed a prior platinum-based chemotherapy regimen will receive glembatumumab vedotin. Glembatumumab vedotin consists of an antibody (a type of human protein) attached to a drug called Monomethyl Auristatin E (MMAE) that can kill cancer cells. Glembatumumab vedotin is intended to work by specifically directing the drug to the cancer cell. It attaches to a molecule on the cancer cell called gpNMB, and then releases the MMAE inside the tumor cell, which in turn causes the cell to die. The purpose of this study is to see whether glembatumumab vedotin is effective in treating people who have advanced or metastatic squamous cell lung cancer that contains gpNMB, to examine how the body handles the drug and the side effects associated with glembatumumab vedotin.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Study of Glembatumumab Vedotin in gpNMB-<span class="go-doc-concept go-doc-keyword">Expressing</span>, Advanced or Metastatic SCC of the Lung

Title

  • Brief Title: Study of Glembatumumab Vedotin in gpNMB-Expressing, Advanced or Metastatic SCC of the Lung
  • Official Title: A Phase I/II Study of Glembatumumab Vedotin in Patients With gpNMB-Expressing, Advanced or Metastatic Squamous Cell Carcinoma of the Lung
  • Clinical Trial IDs

    NCT ID: NCT02713828

    ORG ID: PrE0504

    NCI ID: CDX011-54

    Trial Conditions

    Squamous Cell Carcinoma of the Lung

    Trial Interventions

    Drug Synonyms Arms
    Glembatumumab Vedotin CDX-011; CR011-vcMMAE Phase I
    Glembatumumab Vedotin CDX-011; CR011-vcMMAE Phase II

    Trial Purpose

    Patients with advanced or metastatic, gpNMB-expressing Squamous Cell Carcinoma (SCC) of the
    lung who have failed a prior platinum-based chemotherapy regimen will receive glembatumumab
    vedotin.

    Glembatumumab vedotin consists of an antibody (a type of human protein) attached to a drug
    called Monomethyl Auristatin E (MMAE) that can kill cancer cells. Glembatumumab vedotin is
    intended to work by specifically directing the drug to the cancer cell. It attaches to a
    molecule on the cancer cell called gpNMB, and then releases the MMAE inside the tumor cell,
    which in turn causes the cell to die.

    The purpose of this study is to see whether glembatumumab vedotin is effective in treating
    people who have advanced or metastatic squamous cell lung cancer that contains gpNMB, to
    examine how the body handles the drug and the side effects associated with glembatumumab
    vedotin.

    Detailed Description

    Lung cancer is the most frequent cancer in the world, with annual cases worldwide currently
    estimated at one million and increasing to 10 million by the year 2025. In the United
    States, despite the declining incidence in white males in recent years, lung cancer is still
    the second most frequent cancer in both men (next to prostate) and women (next to breast
    cancer).

    This is an open-label, single arm study of glembatumumab vedotin, a fully-human IgG2
    monoclonal antibody. The activity of glembatumumab vedotin may be greatest in patients who
    overexpress the target, gpNMB.

    This study will include a dose-escalation phase to determine the maximum safe and tolerated
    dose. This will be followed by a 2-stage Phase II expansion. During Phase II Stage 1,
    approximately 20 eligible, treated patients will be enrolled. If 2 patients achieve a
    tumor response [Partial Response (PR) or Complete Response (CR)]; an additional 15 eligible,
    treated patients will be enrolled in Stage 2, for a maximum total of 35 eligible, treated
    patients.

    Glembatumumab vedotin will be administered once every 3 weeks, as a 90-minute intravenous
    (IV) infusion.

    Patients will continue treatment until disease progression or intolerance. Tumor assessments
    will be performed every six (1) weeks for six months, and every nine (2) weeks thereafter,
    until progression.

    A tumor tissue sample (i.e., obtained during a previous procedure or biopsy) will be sent to
    a central laboratory and tested for gpNMB. Research blood samples will also be required.

    Trial Arms

    Name Type Description Interventions
    Phase I Experimental Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Dose-Limiting Toxicity (DLT) evaluation period for determination of the appropriateness of dose-escalation will be through the end of the second treatment cycle. Glembatumumab Vedotin
    Phase II Experimental Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Maximum Tolerated Dose (MTD) determined in Phase I will be used in Phase II. Glembatumumab Vedotin

    Eligibility Criteria

    Inclusion Criteria:

    1. Read, understood, and provided written informed consent and Health Insurance
    Portability and Accountability Act (HIPAA) authorization after the nature of the
    study has been fully explained and must be willing to comply with all study
    requirements and procedures.

    2. Male or female patients with metastatic, histologically- or cytologically-confirmed
    unresectable Stage IIIB or IV non-small cell lung cancer (NSCLC) of squamous
    histology. Mixed histology adenosquamous NSCLC will also be permitted.

    3. Experienced progression/recurrence of disease during or subsequent to the most recent
    anti-cancer regimen.

    4. Any number of prior lines of systemic therapy may have been received for advanced
    (recurrent, locally advanced, or metastatic) SCC of the lung, but at least one must
    have been a platinum-based chemotherapy regimen. Platinum therapy may be given
    on-label or as part of a clinical trial.

    5. Lung cancer confirmed to express gpNMB, as assessed by immunohistochemistry at a
    central lab (using expression in 5% of tumor epithelial cells as a cut-off for
    positivity). This can be tested on archived tissue if available, although preferred
    tumor specimen is a biopsy after the most recent therapy.

    6. Age 18 years.

    7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1.

    8. Measurable disease by RECIST 1.1 criteria. Target lesions selected for tumor
    measurements should be those where surgical resection or radiation are not indicated
    or anticipated.

    9. Resolution of all toxicities related to prior therapies to NCI-CTCAE Grade 1
    severity, except for alopecia, vitiligo, or endocrinopathies on replacement therapy.

    10. Adequate bone marrow function as assessed by absolute neutrophil count (ANC)
    1500/mm3; hemoglobin 9.0 g/dL, and platelet count 100,000/mm3.

    11. Adequate renal function as assessed by serum creatinine 2.0 mg/dL; or calculated or
    24-hour urine creatinine clearance >40 mL/min.

    12. Adequate liver function as assessed by total bilirubin 1.5x upper limit of normal
    (ULN), and alanine transaminase (ALT) and aspartate transaminase (AST) 2.5x ULN (
    5.0x ULN in the case of liver metastases). Patients with known Gilbert's syndrome may
    be enrolled with total bilirubin 3.0 mg/dL.

    13. Both male and female patients of childbearing potential enrolled in this trial must
    use adequate birth control measures during the course of the trial and for at least
    one month after discontinuing study drug.

    14. Willing to provide blood samples for research purposes.

    Exclusion Criteria:

    1. Received glembatumumab vedotin (CR011-vcMMAE; CDX-011) or other MMAE-containing
    agents previously.

    2. Chemotherapy within 21 days or at least 5 half-lives prior to the planned start of
    study treatment; radiation outside the thorax within 14 days prior to the planned
    start of study treatment or thoracic radiation; antibody based therapy or
    investigational therapy within 28 days prior to the planned start of study treatment.

    3. Neuropathy >NCI-CTCAE Grade 1.

    4. Subjects with a history of allergic reactions attributed to compounds of similar
    composition to dolastatin or auristatin. Compounds of similar composition include
    Auristatin PHE as an anti-fungal agent, Auristatin PE (TZT-1027, Soblidotin,
    NSC-654663) as an anti-tumor agent and Symplostatin 1 as an anti-tumor agent.

    5. Known brain metastases, unless previously treated and patients are neurologically
    returned to baseline except for residual signs and symptoms related to Central
    Nervous System (CNS) treatment and CNS lesions are not progressive in size and number
    for 4 weeks.

    6. Significant cardiovascular disease including unstable angina pectoris, uncontrolled
    hypertension, and congestive heart failure related to primary cardiac disease, a
    history of a serious uncontrollable arrhythmia despite treatment, ischemic or severe
    valvular heart disease, or a myocardial infarction within 6 months prior to the trial
    entry.

    7. Active systemic infection requiring treatment. Infection controlled by oral therapy
    will not be exclusionary.

    8. Subjects on immunosuppressive medications such as azathioprine, mycophenolate
    mofetil, cyclosporine or require chronic corticosteroid use (defined as 3 months of
    prednisone dose equivalent of 10 mg).

    9. The MMAE component of glembatumumab vedotin is primarily metabolized by CYP3A.
    Patients taking strong CYP3A inhibitor and inducers are excluded in Phase I (the dose
    escalation portion), to minimize the effect of these modulators on exposure,
    tolerability and dose selection.

    10. History of other malignancy except for adequately treated basal or squamous cell skin
    cancer, curatively treated in situ disease, or any other cancer from which the
    patient has been disease-free for 2 years.

    11. Pregnant or breast-feeding women.

    12. Any underlying medical condition that, in the Investigator's opinion, will make the
    administration of study treatment hazardous to the patient, or would obscure the
    interpretation of adverse events.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Phase I: Number of participants with treatment-related adverse events resulting in dose limiting toxicities (DLTs) as assessed by CTCAE v4.0

    Phase II: Objective Response Rate (ORR)

    Secondary Outcome Measures

    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.

    Duration of Objective Response (DOR)

    Progression-Free Survival (PFS)

    Overall Survival (OS)

    Trial Keywords

    gpNMB-Expressing Squamous Cell Carcinoma of the Lung

    Stage IIIb

    Stage IV

    Advanced Squamous Cell Cancer of the Lung

    Metastatic Squamous Cell Cancer of the Lung

    gpNMB-Expressing

    Glembatumumab Vedotin