Clinical Trials /

Pembrolizumab in Patients With Metastatic Non-squamous Non-small Cell Lung Cancer

NCT02955758

Description:

This phase II trial studies how well pembrolizumab works in treating patients with non-squamous non-small cell lung cancer which has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Patients With Metastatic Non-squamous Non-small Cell Lung Cancer
  • Official Title: A Phase II Trial of Pembrolizumab in Metastatic Non-squamous NSCLC Examining Circulating Tumor DNA Levels as a Surrogate Biomarker of Response

Clinical Trial IDs

  • ORG STUDY ID: LUN0085
  • SECONDARY ID: NCI-2016-01311
  • SECONDARY ID: LUN0085
  • SECONDARY ID: P30CA124435
  • NCT ID: NCT02955758

Conditions

  • Metastatic Non-Squamous Non-Small Cell Lung Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab)

Purpose

This phase II trial studies how well pembrolizumab works in treating patients with non-squamous non-small cell lung cancer which has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To correlate circulating tumor DNA (ctDNA) levels measured using cancer personalized
      profiling by deep sequencing (CAPP-Seq) with radiographic tumor assessments using Response
      Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria in patients with
      metastatic non-squamous non-small cell lung cancer (NSCLC) treated with pembrolizumab.

      SECONDARY OBJECTIVES:

      I. To correlate PD-L1 assessment on pre-treatment tumor samples with objective response
      using RECIST v1.1 criteria in patients with metastatic non-squamous NSCLC treated with
      pembrolizumab.

      II. To determine the overall response rate (ORR) using RECIST v1.1 criteria in patients with
      metastatic non-squamous NSCLC treated with pembrolizumab.

      III. To determine the progression-free survival (PFS) using RECIST v1.1 in patients with
      metastatic non-squamous NSCLC treated with pembrolizumab.

      IV. To determine the overall survival (OS) in patients with metastatic non-squamous NSCLC
      treated with pembrolizumab.

      V. To determine the safety and tolerability of pembrolizumab in patients with metastatic
      non-squamous NSCLC.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Has a pathologically proven recurrent or metastatic non-squamous non-small cell lung
                 cancer
    
              -  Previously received at least one line of prior systemic therapy for metastatic
                 disease; if the patient has a sensitizing EGFR mutation or ALK rearrangement, the
                 patient must have received at least one prior targeted therapy for metastatic disease
                 (ie, EGFR tyrosine kinase inhibitor [TKI] therapy or ALK TKI therapy, respectively);
                 there is no limit on prior therapies allowed; patients must have completed previous
                 treatment (including other investigational therapy) in greater than or equal to the
                 following times prior to initiation of trial treatment:
    
                   -  Anti-cancer monoclonal antibody (mAb) therapy must be completed >= 3 weeks prior
                      to trial treatment
    
                   -  Chemotherapy administered in a daily or weekly schedule must be completed >= 1
                      week prior to trial treatment
    
                   -  Chemotherapy administered in an every 2-week schedule must be completed >= 2
                      weeks prior to trial treatment
    
                   -  Chemotherapy administered in an every 3-week schedule must be completed >= 3
                      weeks prior to trial treatment
    
                   -  Targeted small molecule therapy must be completed >= 1 week prior to trial
                      treatment
    
              -  Prior radiation therapy allowed as long as completed in the following times prior to
                 initiation of trial treatment:
    
                   -  Definitive curative intent radiation >= 3 weeks prior to trial treatment
    
                   -  Palliative body radiation >= 1 week prior to trial treatment
    
                   -  Stereotactic brain radiation >= 1 week prior to trial treatment
    
                   -  Whole brain radiation >= 2 weeks prior to trial treatment
    
              -  Patients with previously treated (with radiation or surgery) brain metastases that
                 are stable are allowed; patients with stable or progressing metastases must have
                 metastases =< 1.5 cm, be asymptomatic, and either not be on steroids or be on 10 mg
                 prednisone equivalent or less
    
              -  Has measurable disease based on RECIST v1.1 criteria
    
              -  Is medically able and willing to undergo needle biopsy of a tumor lesion; PD-L1
                 expression is not required to enroll in the trial
    
              -  Has life expectancy >= 3 months
    
              -  Ability to understand and the willingness to sign a written informed consent document
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
    
              -  Absolute neutrophil count (ANC) >= 1,000/mcL
    
              -  Platelets >= 75,000/mcL
    
              -  Hemoglobin >= 8 g/dL
    
              -  Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated
                 creatinine clearance >= 50 mL/min for patient with creatinine levels > 1.5 x
                 institutional ULN
    
              -  Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for patients with total
                 bilirubin levels > 1.5 ULN
    
              -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
                 alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x
                 ULN OR =< 5 x ULN for patients with liver metastases
    
              -  Female patients of childbearing potential must have a negative urine or serum
                 pregnancy test prior to the first dose of trial treatment; they must also agree to
                 two barrier methods or a barrier method plus a hormonal method, or agree to abstain
                 from heterosexual activity, for the course of the study through 120 days after the
                 last dose of trial treatment; females who have been surgically sterilized or are free
                 from menses for > 1 year (postmenopausal) may enroll
    
              -  Male patients with a female partner of childbearing potential should agree to use a
                 barrier method of contraception, or agree to abstain from heterosexual activity for
                 the course of the study through 120 days after the last dose of trial treatment
    
            Exclusion Criteria:
    
              -  Is currently receiving another investigational therapy
    
              -  Has received prior anti-PD-1 or anti-PD-L1 therapy
    
              -  Has clinically significant toxicities from previous anti-cancer therapy that have not
                 resolved, or have not stabilized at a new baseline
    
              -  Has undergone a surgical procedure involving general anesthesia within 2 weeks of
                 starting trial treatment, or has inadequate healing or recovery from complications of
                 surgery prior to starting trial treatment; this does not apply to low-risk procedures
                 such as thoracentesis; paracentesis; chest tube/pleurX catheter placement; line
                 placement; needle biopsy of tumor; and bronchoscopy
    
              -  Is receiving high dose systemic steroid therapy within 3 days of trial treatment;
                 topical and intra-articular steroid injections are allowed, as are physiologic doses
                 of systemic steroids (=< 10 mg of prednisone equivalent daily)
    
              -  Has carcinomatous meningitis as determined by positive cerebrospinal fluid (CSF)
                 cytology
    
              -  Has known active additional malignancy that is undergoing active treatment
    
              -  Has active autoimmune disease that has required systemic treatment in the past 2
                 years (ie, with use of disease modifying agents, supra-physiologic doses of systemic
                 corticosteroids or immunosuppressive drugs); replacement therapy (eg, thyroxine,
                 insulin; or physiologic corticosteroid replacement therapy for adrenal or pituitary
                 insufficiency, etc.) is not considered a form of systemic treatment; asthma; type I
                 diabetes mellitus; hypothyroidism; and vitiligo are allowed
    
              -  Has a history or current evidence of any condition, therapy, or laboratory
                 abnormality that might confound the results of the trial, interfere with the
                 patient's participation for the full duration of the trial, or is not in the best
                 interest of the patient to participate, in the opinion of the treating investigator;
                 this includes known active tuberculosis; grade 3 active infection; history of
                 allogeneic bone marrow transplant or solid organ transplant; known history of human
                 immunodeficiency virus (HIV); known active hepatitis B (eg, hepatitis [Hep] B
                 deoxyribonucleic acid [DNA] positive in prior 3 months) or known active hepatitis C
                 (eg, hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected in
                 prior 3 months)
    
              -  Known active interstitial lung disease, or current (non-infectious) pneumonitis or
                 history of (non-infectious) pneumonitis that required oral steroids
    
              -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
                 projected duration of the trial, starting with the screening visit through 120 days
                 after the last dose of trial treatment
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:ctDNA levels measured using CAPP-Seq
    Time Frame:Up to 2 years
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events version 4.03
    Time Frame:Up to 2 years
    Safety Issue:
    Description:
    Measure:Overal Response Rate (ORR) defined as proportion of complete responses + partial responses measured using RECIST v1.1 criteria
    Time Frame:Up to 2 years
    Safety Issue:
    Description:
    Measure:Overall Survival (OS)
    Time Frame:From the time of first treatment with pembrolizumab to the time of death, assessed up to 2 years
    Safety Issue:
    Description:
    Measure:PD-L1 assessment on pre-treatment tumor samples assess in tumor tissue by immunohistochemistry
    Time Frame:Up to 2 years
    Safety Issue:
    Description:
    Measure:PFS measured using RECIST v1.1 criteria
    Time Frame:From the time of first treatment with pembrolizumab to the time of progression or death from any cause, whichever comes earlier, assessed up to 2 years
    Safety Issue:
    Description:

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Joel Neal

    Last Updated

    February 21, 2017