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
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).
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
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
≥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
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
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
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
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
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
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.