Clinical Trials /

Study of AGEN1884 With Pembrolizumab in 1L NSCLC

NCT03411473

Description:

A Phase IIa Open-Label Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of AGEN1884 in Combination with Pembrolizumab in Subjects with Chemotherapy Naïve, PD-L1 high, metastatic Non-Small Cell Lung Cancer (NSCLC)

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

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of AGEN1884 With Pembrolizumab in 1L NSCLC
  • Official Title: A Phase IIa Open-Label Trial of AGEN1884 in Combination With Pembrolizumab in Subjects With Chemotherapy Naïve, PD-L1 High, Metastatic Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: C-500-03
  • NCT ID: NCT03411473

Conditions

  • NSCLC Stage IV

Interventions

DrugSynonymsArms
AGEN1884 in combination with pembrolizumabAGEN1884 with pembrolizumab

Purpose

A Phase IIa Open-Label Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of AGEN1884 in Combination with Pembrolizumab in Subjects with Chemotherapy Naïve, PD-L1 high, metastatic Non-Small Cell Lung Cancer (NSCLC)

Detailed Description

      This is a Phase IIa, open-label study, of AGEN1884 in combination with pembrolizumab in
      subjects with stage IV NSCLC whose tumors have high PD-L1 expression and no EGFR or ALK
      genomic tumor aberrations.

      The study consists in two phases:

        -  Safety Run-in Phase

        -  Efficacy Phase

      Subjects will be enrolled in a "3+3" Safety Run-in followed by enrollment completing the
      efficacy cohort. Two different dose levels of AGEN1884 may be tested in combination with the
      approved pembrolizumab treatment for this indication (until disease progression, unacceptable
      toxicity, or up to a maximum of 24 months). Each subject will stay on the dose level assigned
      at trial entry.
    

Trial Arms

NameTypeDescriptionInterventions
AGEN1884 with pembrolizumabExperimentalAGEN1884 in combination with pembrolizumab

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Voluntarily agree to participate.
    
              2. Be ≥18 years of age.
    
              3. Have a histologically or cytologically confirmed diagnosis of NSCLC, is stage IV, does
                 not have an EGFR sensitizing (activating) mutation or ALK translocation, and has not
                 received prior systemic chemotherapy treatment for their metastatic NSCLC.
    
              4. Have measurable disease based on RECIST 1.1 as determined by the site.
    
              5. Have a life expectancy of at least 3 months and a performance status of 0 or 1 on the
                 Eastern Cooperative Oncology Group (ECOG) Performance Status
    
              6. Have adequate organ function as indicated by the following laboratory values:
    
                   1. Adequate hematological function defined by absolute neutrophil count (ANC) > 1.5
                      x 109/L, platelet count > 100 x 109/L, and hemoglobin > 9 g/dL (without
                      transfusions within 2 weeks of first dose).
    
                   2. Adequate hepatic function based by a total bilirubin level < the institutional
                      upper limit of normal (IULN), aspartate aminotransferase (AST) level < 1.5 x
                      IULN, alanine aminotransferase (ALT) level < 1.5 x IULN, and alkaline phosphatase
                      ≤ 2.5 ULN.
    
                   3. Adequate renal function defined as Creatinine ≤ 1.5 x IULN OR calculated
                      creatinine clearance > 60 mL/min for subjects with creatinine levels > 1.5 x IULN
                      (If no local guideline is available, creatinine clearance should be calculated
                      using the Cockcroft-Gault Method).
    
                   4. Adequate coagulation defined by international normalized ratio (INR) or
                      prothrombin time ≤ 1.5 x IULN (unless the subject is receiving anticoagulant
                      therapy); and activated partial thromboplastin time (aPTT) ≤ 1.5 x IULN (unless
                      the subject is receiving anticoagulant therapy)
    
                   5. Adequate endocrine function defined by thyroid stimulating hormone (TSH) within
                      normal limits. Note: if TSH is not within normal limits at baseline, the subject
                      may still be eligible if T3 and free T4 are within normal limits.
    
              7. Subject has no history of prior malignancy, with the exception of basal cell carcinoma
                 of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ
                 cervical cancer, or has undergone potentially curative therapy with no evidence of
                 that disease recurrence for 5 years since initiation of that therapy.
    
              8. Have provided a formalin fixed tumor tissue sample from a biopsy of a tumor lesion
                 either at the time of or after the diagnosis of metastatic disease has been made AND
                 from a site not previously irradiated to assess for PD-L1 status.
    
              9. The subject's tumor does not harbor an EGFR sensitizing (activating) mutation or ALK
                 translocation.
    
             10. The subject's tumor must have high PD-L1 expression (TPS ≥50%) as determined by an
                 FDA-approved test.
    
             11. Female subjects must have a negative serum pregnancy test at screening (within 72
                 hours of first dose of study medication) if of childbearing potential or be of
                 non-child bearing potential.
    
             12. If of childbearing potential, female subjects must be willing to use two adequate
                 barrier methods throughout the study, starting with the screening visit through 120
                 days after the last dose of study therapy.
    
             13. Male subjects with a female partner(s) of child-bearing potential must agree to use
                 two adequate barrier methods throughout the trial starting with the screening visit
                 through 120 days after the last dose of pembrolizumab is received. Males with pregnant
                 partners must agree to use a condom; no additional method of contraception is required
                 for the pregnant partner.
    
             14. Subject is willing and able to comply with the requirements of the protocol.
    
            Exclusion Criteria:
    
              1. Has an EGFR sensitizing mutation and/or an ALK translocation.
    
              2. Has received systemic therapy for the treatment of their stage IV NSCLC. Completion of
                 treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy
                 is allowed as long as therapy was completed at least 6 months prior to the diagnosis
                 of metastatic disease.
    
              3. Is currently participating and receiving study therapy or has participated in a study
                 of an investigational agent and received study therapy or used an investigation device
                 within 4 weeks of the first dose of treatment.
    
              4. Is receiving systemic steroid therapy < 3 days prior to the first dose of trial
                 treatment or receiving any other form of immunosuppressive medication.
    
              5. Is expected to require any other form of systemic or localized antineoplastic therapy
                 while on trial (including maintenance therapy with another agent for NSCLC, radiation
                 therapy, and/or surgical resection)
    
              6. Has received prior systemic cytotoxic chemotherapy, biological therapy, OR major
                 surgery within 3 weeks of the first dose of trial treatment; received thoracic
                 radiation therapy of > 30 Gy within 6 months of the first dose of trial treatment.
    
              7. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
                 anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
                 ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
                 or checkpoint pathways).
    
              8. Has central nervous system (CNS) metastases and/or carcinomatous meningitis identified
                 either on the baseline brain imaging obtained during the screening period OR
                 identified prior to signing the ICF.
    
              9. Active autoimmune disease that has required systemic treatment in past 2 years (i.e.
                 with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
                 Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid
                 replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
                 form of systemic treatment.
    
             10. Has had an allogeneic tissue/solid organ transplant.
    
             11. Has interstitial lung disease (ILD) OR has had a history of pneumonitis that has
                 required oral or IV steroids.
    
             12. Has received or will receive a live vaccine within 30 days prior to the first
                 administration of study medication. Seasonal flu vaccines that do not contain a live
                 virus are permitted
    
             13. Has an active infection requiring intravenous systemic therapy.
    
             14. Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
    
             15. Has known active Hepatitis B, Hepatitis C or tuberculosis.
    
             16. Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular
                 accident/stroke or myocardial infarction within 6 months of enrollment, unstable
                 angina, congestive heart failure (New York Heart Association class ≥II), or serious
                 uncontrolled cardiac arrhythmia requiring medication.
    
             17. Has a history or current evidence of any condition, therapy, or laboratory abnormality
                 that might confound the results of the trial, interfere with the subject's
                 participation for the full duration of the trial, or is not in the best interest of
                 the subject to participate, in the opinion of the treating Investigator.
    
             18. Has known psychiatric or substance abuse disorders that would interfere with
                 cooperation with the requirements of the trial.
    
             19. Is, at the time of signing informed consent, a regular user (including "recreational
                 use") of any illicit drugs or had a recent history (within the last year) of substance
                 abuse (including alcohol).
    
             20. Is pregnant or breastfeeding, or expecting to conceive or father children within the
                 projected duration of the trial, starting with the screening visit (Visit 1) through
                 120 days after the last dose of pembrolizumab or AGEN1884.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Occurrence of DLTs in subjects in the Safety Run-in Phase of the trial
    Time Frame:21 days
    Safety Issue:
    Description:Occurrence of DLTs in subjects in the Safety Run-in Phase of the trial

    Secondary Outcome Measures

    Measure:Frequency, severity, and duration of treatment-emergent AEs (TEAEs)
    Time Frame:116 weeks
    Safety Issue:
    Description:Frequency, severity, and duration of treatment-emergent AEs (TEAEs)
    Measure:Frequency, severity, and duration of treatment-related AEs
    Time Frame:116 weeks
    Safety Issue:
    Description:Frequency, severity, and duration of treatment-related AEs
    Measure:Confirmed BOR per RECIST 1.1
    Time Frame:116 weeks
    Safety Issue:
    Description:Confirmed BOR per RECIST 1.1
    Measure:Duration of response per RECIST 1.1
    Time Frame:36 months
    Safety Issue:
    Description:Duration of response per RECIST 1.1
    Measure:PFS time
    Time Frame:36 months
    Safety Issue:
    Description:PFS time
    Measure:OS time
    Time Frame:June 2020 ( When 14 patients have completed 2 years of treatment)
    Safety Issue:
    Description:OS time
    Measure:Unconfirmed response at 12 weeks from first dose per RECIST 1.1
    Time Frame:Up to 24 months from 1st dose of treatment
    Safety Issue:
    Description:Unconfirmed response at 12 weeks from first dose per RECIST 1.1
    Measure:Pharmacokinetic profile of AGEN1884 and pembrolizumab
    Time Frame:At least 20 patients have completed 12 weeks from 1st dose of treatment
    Safety Issue:
    Description:Pharmacokinetic profile of AGEN1884 and pembrolizumab
    Measure:Immunogenicity of AGEN1884 and pembrolizumab
    Time Frame:All patients on study have completed 6 weeks from 1st dose of treatment
    Safety Issue:
    Description:Immunogenicity of AGEN1884 and pembrolizumab

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Agenus Inc.

    Last Updated

    April 6, 2018