Clinical Trials /

A Study in Subjects With Advanced Solid Tumors

NCT04156100

Description:

This study is an open-label, Phase 1 study to evaluate the safety, tolerability, PK, and pharmacodynamic profiles of AGEN1223 and to assess the maximum tolerated dose (MTD) in subjects with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study in Subjects With Advanced Solid Tumors
  • Official Title: A Phase 1 Study of AGEN1223, a Bispecific Antibody in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: C-900-01
  • NCT ID: NCT04156100

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
AGEN1223AGEN1223

Purpose

This study is an open-label, Phase 1 study to evaluate the safety, tolerability, PK, and pharmacodynamic profiles of AGEN1223 and to assess the maximum tolerated dose (MTD) in subjects with advanced solid tumors.

Detailed Description

      This study is an open-label, Phase 1 study to evaluate the safety, tolerability, PK, and
      pharmacodynamic profiles of AGEN1223 and to assess the maximum tolerated dose (MTD) in
      subjects with advanced solid tumors. This monotherapy study will also determine the RP2D of
      the monotherapy. This Phase 1 study will be conducted in an accelerated titration (for the
      first two dosing cohorts) and standard 3+3 dose escalation format. AGEN1223 will be
      administered on Day 1 of each 3-week cycle for 2 years or until any progressive disease (PD)
      or unacceptable toxicity is reported. The safe starting dose will be at the estimated
      minimally anticipated biological effect level (MABEL). The treatment phase is divided into
      3-week cycles with associated evaluations and procedures that must be performed at specific
      timepoints. Tumor assessments will be conducted every 6 weeks (±3 days) from first dose until
      treatment discontinuation. Each cycle begins with the administration of AGEN1223 on Day 1 of
      a 3-week cycle (timing of doses may be adjusted for management of adverse events [AEs]).
      Subjects will be treated for up to 2 years or until PD or unacceptable toxicity occurs. A
      Safety Monitoring Committee (SMC) will be established to assess safety and decide on dose
      escalation
    

Trial Arms

NameTypeDescriptionInterventions
AGEN1223Experimental
  • AGEN1223

Eligibility Criteria

        Inclusion Criteria:

          1. Voluntarily agree to participate by giving written informed consent (participation in
             genetic testing is optional)

          2. Greater than or equal to 18 years of age

          3. Histologically or cytologically confirmed diagnosis of an advanced solid tumor for
             which no standard therapy is available or standard therapy has failed.

          4. Measurable disease on baseline imaging based on RECIST 1.1.

          5. Life expectancy of at least 3 months and an Eastern Cooperative Oncology Group (ECOG)
             performance status of 0 or 1.

          6. Adequate organ function as indicated by the following laboratory values:

               -  Adequate hematological function, defined as absolute neutrophil count (ANC)
                  ≥1500/μL, platelet count ≥100,000/μL, and hemoglobin ≥8 g/dL without recent
                  transfusion (defined as a transfusion that has occurred within 2 weeks of the
                  hemoglobin measurement).

               -  Adequate hepatic function based by a total bilirubin level ≤1.5 × the
                  institutional upper limit of normal (IULN), aspartate aminotransferase (AST)
                  level ≤2.5 × IULN, alanine aminotransferase (ALT) level ≤2.5 × IULN.

               -  Adequate renal function defined as creatinine ≤1.5 × IULN OR measured or
                  calculated creatinine clearance >40 ml/min per institutional standard. Assessment
                  methods should be recorded.

               -  Adequate coagulation defined by international normalized ratio (INR) or
                  prothrombin time ≤1.5 × IULN and activated partial thromboplastin time (aPTT)
                  ≤1.5 × IULN (unless the subject is receiving anticoagulant therapy)

          7. No history of prior or concomitant malignancy, with the exception of resected basal
             cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the
             skin, and in situ cervical cancer or other malignancies that have undergone
             potentially curative therapy with no evidence of disease recurrence for 5 years since
             initiation of that therapy.

        8 Subjects must provide a sufficient and adequate formalin-fixed paraffin embedded (FFPE)
        tumor tissue sample preferably from the most recent biopsy of a tumor lesion, collected
        either at the time of or after the diagnosis of advanced or metastatic disease has been
        made AND from a site not previously irradiated. If no tumor tissue is available, a fresh
        biopsy will be required.

        9. Female subjects of child-bearing potential must have a negative serum pregnancy test at
        screening (within 72 hours of first dose of study medication). Non-childbearing potential
        is defined as:

          -  ≥45 years of age and has not had menses for greater than 1 year,

          -  Amenorrheic for ≥2 years without a hysterectomy and oophorectomy and a
             folliclestimulating hormone (FSH) value in the postmenopausal range upon pretrial
             (screening) evaluation,

          -  Whose status is post hysterectomy, oophorectomy, or tubal ligation. 10. Female
             subjects of child-bearing potential must be willing to use highly effective
             contraceptive measures starting with the screening visit through 120 days after the
             last dose of study treatment.

        Note: Abstinence is acceptable if this is the established and preferred contraception for
        the subject.

        11. Male subjects with a female partner(s) of child-bearing potential must agree to use
        highly effective contraceptive measures throughout the trial starting with the screening
        visit through 120 days after the last dose of study treatment is received. Males with
        pregnant partners must agree to use a condom; no additional method of contraception is
        required for the pregnant partner.

        Note: Abstinence is acceptable if this is the established and preferred contraception
        method for the subject.

        12. Willing and able to comply with the requirements of the protocol.

        Exclusion Criteria:

          1. 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 3 weeks of the first dose of current study drug.

          2. Prior therapy with any monoclonal antibody (mAb) or agent binding the same targets as
             AGEN1223.

          3. Systemic cytotoxic chemotherapy, biological therapy, or major surgery within 3 weeks
             prior to first dose of study drug; a 1-week washout is permitted for palliative
             radiation to non-central nervous system (CNS) disease with Sponsor approval.

          4. Persisting toxicity with Grade >1 severity related to prior therapy based on National
             Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0
             (NCI-CTCAE).

             Note: Sensory neuropathy or alopecia of Grade ≤2 is acceptable.

          5. Is expected to require any other form of systemic or localized antineoplastic therapy
             while on trial (including maintenance therapy with another agent, radiation therapy,
             and/or surgical resection).

          6. Known severe hypersensitivity reactions (NCI-CTCAE Grade ≥3) to fully human mAbs or
             severe reaction to immuno-oncology agents, such as colitis or pneumonitis, requiring
             treatment with steroids, or has a history of interstitial lung disease (ILD), any
             history of anaphylaxis, or uncontrolled asthma.

          7. Systemic corticosteroid therapy 1 week prior to the first dose of study drug or
             receiving any other form of systemic immunosuppressive medication (corticosteroid use
             as a premedication for intravenous (IV) contrast allergies/reactions is allowed).
             Subjects who are receiving daily corticosteroid replacement therapy are an exception
             to this rule. Daily prednisone at doses of up to 7.5 mg or equivalent hydrocortisone
             dose are examples of permitted replacement therapy.

          8. CNS tumor, metastasis(es), and/or carcinomatous meningitis identified either on the
             baseline brain imaging obtained during the screening period or identified prior to
             consent.

             Note: Subjects with history of brain metastases that have been treated may participate
             provided they show evidence of stable supra-tentorial lesions at screening (defined as
             2 brain images, both of which are obtained after treatment to the brain metastases.
             These imaging scans should both be obtained ≥4 weeks apart). In addition, any
             neurologic symptoms that developed either as a result of the brain metastases or their
             treatment must have returned to baseline or resolved. Any steroids administered as
             part of this therapy must be completed ≥3 days prior to the first dose of study
             medication.

          9. Active or history of autoimmune disease that has required systemic treatment within 2
             years of the start of trial treatment (i.e., with use of disease-modifying agents,
             corticosteroids, or immunosuppressive drugs).

             Note: Subjects with diabetes type 1, vitiligo, psoriasis, hypo-, or hyperthyroid
             disease not requiring immunosuppressive treatment are eligible.

         10. Allogeneic tissue/solid organ transplant.

         11. ILD OR has had a history of pneumonitis that has required oral or IV corticosteroids.

         12. Active infection requiring treatment.

         13. History of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).

         14. Active hepatitis B and/or hepatitis C virus (HBV and HCV).

         15. 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.

         16. 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.

         17. Psychiatric or substance abuse disorders that would interfere with cooperation with
             the requirements of the trial.

         18. Legally incapacitated or has limited legal capacity.

         19. Pregnant or breastfeeding.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity (DLT)
Time Frame:First 28 days of treatment
Safety Issue:
Description:In subjects in dose escalation

Secondary Outcome Measures

Measure:Frequency, severity, and duration of treatment-emergent AEs (TEAEs)
Time Frame:Screening through 90 days after last dose
Safety Issue:
Description:For all dose groups according to NCI-CTCAE Version 5.0
Measure:Maximum observed concentration at steady state (Cmax-ss)
Time Frame:From first dose through 1 year of treatment
Safety Issue:
Description:PK Profile of AGEN1223
Measure:Minimum observed concentration at steady state (Cmin-ss)
Time Frame:From first dose through 1 year of treatment
Safety Issue:
Description:PK Profile of AGEN1223
Measure:area under the plasma/serum concentration-time curve within time span t1 to t2 at steady-state (AUC(t1-t2)-ss)
Time Frame:From first dose through 1 year of treatment
Safety Issue:
Description:PK Profile of AGEN1223
Measure:area under the plasma/serum concentration-time curve from time zero to time t (AUC(0-t))
Time Frame:From first dose through 1 year of treatment
Safety Issue:
Description:PK Profile of AGEN1223
Measure:area under the plasma/serum concentration-time curve from time zero to infinity (AUC(0-∞))
Time Frame:From first dose through 1 year of treatment
Safety Issue:
Description:PK Profile of AGEN1223
Measure:time to maximum observed concentration (tmax)
Time Frame:From first dose through 1 year of treatment
Safety Issue:
Description:PK Profile of AGEN1223
Measure:terminal disposition rate constant (λz)
Time Frame:From first dose through 1 year of treatment
Safety Issue:
Description:PK Profile of AGEN1223
Measure:terminal elimination half-life (t1/2)
Time Frame:From first dose through 1 year of treatment
Safety Issue:
Description:PK Profile of AGEN1223
Measure:systemic clearance (CL)
Time Frame:From first dose through 1 year of treatment
Safety Issue:
Description:PK Profile of AGEN1223
Measure:volume of distribution (Vd).
Time Frame:From first dose through 1 year of treatment
Safety Issue:
Description:PK Profile of AGEN1223
Measure:Immunogenicity of AGEN1223
Time Frame:From first dose through 1 year of treatment
Safety Issue:
Description:
Measure:Overall Response Rate
Time Frame:Screening up to 2 years of treatment
Safety Issue:
Description:Per RECIST 1.1 based on Investigator assessment
Measure:Duration of Response
Time Frame:Screening up to 2 years of treatment
Safety Issue:
Description:Per RECIST 1.1 based on Investigator assessment
Measure:Disease Control Rate
Time Frame:Screening up to 2 years of treatment
Safety Issue:
Description:Including complete and partial responders and stable disease (SD) for at least 12 weeks, per RECIST 1.1 based on Investigator assessment.
Measure:Progression-free Survival median and/or rate
Time Frame:Screening up to 2 years of treatment
Safety Issue:
Description:As defined in the Statistical Analysis Plan

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Agenus Inc.

Last Updated

November 5, 2019