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
  • AGEN1884 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:Terminated
Lead Sponsor:Agenus Inc.

Last Updated

June 2, 2020