Clinical Trials /

A Study in Subjects With Advanced Cancer

NCT04121676

Description:

This is a Phase I open-label, 3+3 dose escalation design Phase I trial to assess the safety, tolerability and dose-limiting toxicity (DLT) of AGEN2373 as monotherapy in subjects with 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 Cancer
  • Official Title: A Phase 1 Study of AGEN2373, an Anti-CD137 Monoclonal Antibody, in Subjects With Advanced Cancer

Clinical Trial IDs

  • ORG STUDY ID: C-1100-01
  • NCT ID: NCT04121676

Conditions

  • Advanced Cancer

Interventions

DrugSynonymsArms
AGEN2373AGEN2373

Purpose

This is a Phase I open-label, 3+3 dose escalation design Phase I trial to assess the safety, tolerability and dose-limiting toxicity (DLT) of AGEN2373 as monotherapy in subjects with solid tumors.

Detailed Description

      This is a Phase I open-label, dose escalation study of AGEN2373, an Anti-CD137 Monoclonal
      Antibody being assessed as monotherapy in subjects with solid tumors. The study is a 3+3 dose
      escalation design and the maximum recommended starting dose (RSD) was derived from the
      minimally anticipated biological effect level (MABEL). AGEN2373 will be administered via
      continuous IV infusion on Day 1 of each 4-week cycle for up to 2 years or until disease
      progression or unacceptable toxicity. The primary objectives are to assess the safety,
      tolerability, and DLT of AGEN2373 as monotherapy in subjects with advanced solid tumors and
      to determine the recommended Phase 2 dose (RP2D).
    

Trial Arms

NameTypeDescriptionInterventions
AGEN2373Experimental
  • AGEN2373

Eligibility Criteria

        Inclusion Criteria:

          1. Voluntarily agree to participate by giving written informed consent. Participation in
             pharmacogenomics (PGx) testing is optional.

          2. ≥18 years of age.

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

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

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

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

               1. 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).

               2. Adequate hepatic function, defined as total bilirubin level ≤1.5 x institutional
                  upper limit of normal (IULN), aspartate aminotransferase (AST) ≤2.5 x IULN, and
                  alanine aminotransferase (ALT) ≤2.5 x IULN.

               3. Adequate renal function defined as creatinine ≤1.5 x IULN OR calculated
                  creatinine clearance

                  ≥40 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 as international normalized ratio (INR) or
                  prothrombin time ≤1.5 x IULN and activated partial thromboplastin time (aPTT)
                  ≤1.5 x IULN (unless subject 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 childbearing 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 1 of the following: a ≥45 years of age and has not had menses
             for >1 year. b. Amenorrheic for >2 years without a hysterectomy and oophorectomy and
             follicle-stimulating hormone value in the postmenopausal range upon pretrial
             (screening) evaluation. c. Status is post-hysterectomy, -oophorectomy, or -tubal
             ligation.

         10. Female subjects of childbearing potential must be willing to use highly effective
             contraceptive measures starting with the screening visit through 90 days after 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 childbearing potential must
        agree to use highly effective contraceptive measures throughout the trial starting with the
        screening visit through 90 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 first dose of current trial treatment.

          2. Received prior systemic cytotoxic chemotherapy, biological therapy, or major surgery
             within 3 weeks prior to first dose of trial treatment. A 1-week washout is permitted
             for palliative radiation to non-central nervous system (CNS) disease, with sponsor
             approval.

          3. Received prior therapy with any anti-CD137 monoclonal antibody or agent.

          4. Persistent toxicity of National Cancer Institute Common Terminology Criteria for
             Adverse Events (NCI-CTCAE) Grade >1 severity that is related to prior therapy. Note:
             Sensory neuropathy or alopecia of Grade ≤2 is acceptable.

          5. 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 (Grade ≥3) hypersensitivity reactions to monoclonal antibodies, antibody,
             or severe reaction to immuno-oncology agents, such as colitis or pneumonitis requiring
             treatment with steroids; or current or history of interstitial lung disease,
             anaphylaxis, uncontrolled asthma, (i.e., ≥3 features of partly controlled asthma) or
             pneumonitis that has required oral or intravenous (IV) corticosteroids.

          7. Receiving systemic corticosteroid therapy 1 week prior to the first dose of trial
             treatment or receiving any other form of systemic immunosuppressive medication.
             Corticosteroid use as a premedication for IV contrast allergies/reactions is allowed.
             Subjects who are receiving daily corticosteroid replacement therapy are also an
             exception to this rule. Daily prednisone at doses of

             ≤7.5 mg or equivalent hydrocortisone dose are examples of permitted replacement
             therapy. Use of inhaled or topical corticosteroids is permitted.

          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 and
             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 first dose of trial medication.

          9. Active or history of autoimmune disease that requires 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, or hypo- or hyperthyroid disease not requiring immunosuppressive
             treatment are eligible.

         10. Has had an allogeneic tissue/solid organ transplant.

         11. Active infection requiring treatment.

         12. Known history of human immunodeficiency virus (HIV) type 1 or 2 antibodies.

         13. Current or chronic infection with hepatitis B and/or hepatitis C virus defined as:

             • Positive test for hepatitis B surface antigen (HBsAg) indicating active or chronic
             infection.

             Note: Patients with previous history of hepatitis B (who have cleared the infection
             and have natural immunity, i.e. hepatitis B core antibody positive cases) are excluded
             if prophylaxis against hepatitis B reactivation with antiviral agents is recommended.

             • Positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating active or
             chronic infection. Note: Subjects with positive hepatitis C antibody and negative
             hepatitis C by polymerase chain reaction (PCR) are eligible.

         14. 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.

         15. 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.

         16. Known psychiatric or substance abuse disorder that would interfere with cooperation
             with the requirements of the trial.

         17. Legally incapacitated or has limited legal capacity.

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

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:Frequency of treatment-emergent adverse events (TEAEs)
Time Frame:Screening to 90 days from last dose
Safety Issue:
Description:According to NCI-CTCAE Version 5.0
Measure:Severity of treatment-emergent adverse events (TEAEs)
Time Frame:Screening to 90 days from last dose
Safety Issue:
Description:According to NCI-CTCAE Version 5.0
Measure:Duration of treatment-emergent adverse events (TEAEs)
Time Frame:Screening to 90 days from last dose
Safety Issue:
Description:According to NCI-CTCAE Version 5.0
Measure:Maximum observed concentration at steady state (Cmax-ss)
Time Frame:Day 1 of dosing through 90 days from the last dose
Safety Issue:
Description:PK Profile of AGEN2373
Measure:Minimum observed concentration at steady state (Cmin-ss)
Time Frame:Day 1 of dosing through 90 days from the last dose
Safety Issue:
Description:PK Profile of AGEN2373
Measure:area under the plasma/serum concentration-time curve within time span t1 to t2 at steady-state (AUC(t1-t2)-ss)
Time Frame:Day 1 of dosing through 90 days from the last dose
Safety Issue:
Description:PK Profile of AGEN2373
Measure:area under the plasma/serum concentration-time curve from time zero to time t (AUC(0-t))
Time Frame:Day 1 of dosing through 90 days from the last dose
Safety Issue:
Description:PK Profile of AGEN2373
Measure:area under the plasma/serum concentration-time curve from time zero to infinity (AUC(0-∞))
Time Frame:Day 1 of dosing through 90 days from the last dose
Safety Issue:
Description:PK Profile of AGEN2373
Measure:time to maximum observed concentration (tmax)
Time Frame:Day 1 of dosing through 90 days from the last dose
Safety Issue:
Description:PK Profile of AGEN2373
Measure:terminal disposition rate constant (λz)
Time Frame:Day 1 of dosing through 90 days from the last dose
Safety Issue:
Description:PK Profile of AGEN2373
Measure:terminal elimination half-life (t1/2)
Time Frame:Day 1 of dosing through 90 days from the last dose
Safety Issue:
Description:PK Profile of AGEN2373
Measure:systemic clearance (CL)
Time Frame:Day 1 of dosing through 90 days from the last dose
Safety Issue:
Description:PK Profile of AGEN2373
Measure:volume of distribution (Vd).
Time Frame:Day 1 of dosing through 90 days from the last dose
Safety Issue:
Description:PK Profile of AGEN2373
Measure:Immunogenicity of AGEN2373
Time Frame:Pre-dose through 3 months after the last dose.
Safety Issue:
Description:
Measure:Overall Response Rate (ORR)
Time Frame:Evaluated throughout the protocol up to 2 years
Safety Issue:
Description:per RECIST 1.1
Measure:Duration of Response (DOR)
Time Frame:First observation of documented disease progression (or death within 12 weeks of the last tumor assessment).
Safety Issue:
Description:per RECIST 1.1
Measure:Disease Control Rate (DCR)
Time Frame:24 weeks of first dose
Safety Issue:
Description:including complete and partial responders and stable disease [SD] for at least 12 weeks per RECIST 1.1
Measure:Progression Free Survival (PFS)
Time Frame:First treatment administration to first observation of documented disease progression (or death within 12 weeks of last tumor assessment).
Safety Issue:
Description:median and/or rate as defined in the statistical analysis plan

Details

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

Last Updated

November 20, 2019