MC# 19-27 - A Phase I Study of AGEN2373, an Anti-CD137 Monoclonal Antibody in Subjects with Advanced Cancer

  • Agent(s): AGEN2373
  • Disease Type(s): Solid Tumor
  • Phase(s): I
  • Drug Classification(s): Targeted Therapy, Immunotherapy, Monoclonal Antibody
  • Molecular Target(s): CD137

Mechanism of Action

AGEN2373 is a fully human monoclonal antibody that boosts the immune response to cancer cells by enhancing CD137 co-stimulatory signaling in activated immune cells.  Importantly, the unique binding properties of AGEN2373 are expected to limit its activity outside of the tumor site and mitigate toxicities that may be associated with systemic activation of CD137 in humans.

Purpose

In this study, the sponsor and investigators want to learn:

  • How much of AGEN2373 can be given with an acceptable level of side effects
  • About the safety and tolerability of AGEN2373
  • How proteins that indicate the status of your disease are affected with use of AGEN2373
  • How much of AGEN2373 is absorbed into the blood and how fast it is removed
  • If research tests can be used in the future to predict who will benefit from AGEN2373
  • If your body develops proteins that work against AGEN2373
Inclusion Criteria
  • Voluntarily agree to participate by giving written informed consent.  Participation in PGx testing is optional.
  • ≥18 years of age
  • Histologically or cytologically confirmed diagnosis of metastatic or locally advanced solid tumor for which no standard therapy is available or standard therapy has failed
  • Measurable disease on imaging based on RECIST 1.1
  • Life expectancy of ≥3 months and ECOG performance status of 0 or 1
  • Adequate organ function, as indicated by the following laboratory values:
    • Adequate hematological function, defined as 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, defined as total bilirubin level ≤1.5 x institutional upper limit of normal (IULN), AST ≤2.5 x IULN, and ALT ≤2.5 x IULN
    • 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)
    • 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)
  • 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
  • Subjects must provide a sufficient and adequate 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. 
  • 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:
    • ≥45 years of age and has not had menses for >1 year
    • Amenorrheic for >2 years without a hysterectomy and oophorectomy and follicle- stimulating hormone value in the postmenopausal range upon pretrial (screening) evaluation
    • Status is post-hysterectomy, -oophorectomy, or –tubal ligation
  • 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
  • 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
  • Willing and able to comply with the requirements of the protocol
Exclusion Criteria
  • 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
  • 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.
  • Received prior therapy with any anti–CD137 monoclonal antibody or agent
  • Persistent toxicity of NCI-CTCAE Grade >1 severity that is related to prior therapy
    • Note: Sensory neuropathy or alopecia of Grade ≤2 is acceptable
  • 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)
  • 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 IV corticosteroids
  • 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 ≤5 mg or equivalent hydrocortisone dose are examples of permitted replacement therapy.  Use of inhaled or topical corticosteroid is permitted.
  • 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.
  • 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
  • Has had an allogeneic tissue/solid organ transplant
  • Active infection requiring treatment
  • Known history of HIV type 1 or 2 antibodies
  • 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 (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
  • 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
  • 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
  • Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
  • Legally incapacitated or has limited legal capacity
  • Pregnant or breastfeeding

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City

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Re: MC# 19-27