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

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

  • ORG STUDY ID: PrE0504
  • SECONDARY ID: CDX011-54
  • NCT ID: NCT02713828

Conditions

  • Squamous Cell Carcinoma of the Lung

Interventions

DrugSynonymsArms
Phase I: Glembatumumab VedotinCDX-011; CR011-vcMMAEPhase I: Glembatumumab Vedotin
Phase II: Glembatumumab VedotinCDX-011; CR011-vcMMAEPhase II: Glembatumumab Vedotin

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

NameTypeDescriptionInterventions
Phase I: Glembatumumab VedotinExperimentalGlembatumumab 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.
  • Phase I: Glembatumumab Vedotin
Phase II: Glembatumumab VedotinExperimentalGlembatumumab 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.
  • 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
             (Staging per American Joint Committee on Cancer [AJCC], Edition 7). 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. Serum albumin ≥ 3 g/dL.

         13. 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.

         14. 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.

         15. 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. Subjects must not be on home oxygen therapy (intermittent or continuous).

         13. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: Determine Maximum Tolerated Dose (MTD)
Time Frame:42 (±3) days
Safety Issue:
Description:To determine the Maximum Tolerated Dose (MTD) by number of participants with DLTs.

Secondary Outcome Measures

Measure:Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0.
Time Frame:23 months
Safety Issue:
Description:To further characterize the safety of glembatumumab vedotin by the number of participants with abnormal laboratory values and/or adverse events related to treatment (including Serious Adverse Events and Other Adverse Events).
Measure:Duration of Objective Response (DOR)
Time Frame:23 months
Safety Issue:
Description:DOR assessed in accordance with RECIST 1.1.
Measure:Progression-Free Survival (PFS)
Time Frame:23 months
Safety Issue:
Description:PFS assessed in accordance with RECIST 1.1.
Measure:Overall Survival (OS)
Time Frame:23 months
Safety Issue:
Description:OS assessed in accordance with RECIST 1.1.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:PrECOG, LLC.

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

Last Updated

July 16, 2019