This study is an open-label, Phase 1, multicenter study to evaluate the safety, tolerability,
PK, and PD profiles of AGEN2373 as a monotherapy and in combination with Balstilimab
(AGEN2034), and to assess the maximum tolerated dose (MTD) in subjects with advanced solid
tumors.
This Phase 1 study will enroll up to approximately 86 evaluable adult subjects with
refractory cancer (solid tumors) regardless of diagnosis. Subjects may be enrolled into the
following cohorts:
The trial will consist of a 3+3 dose escalation that will evaluate different combination dose
levels of AGEN2373 monotherapy and in combination with Balstilimab (AGEN2034). Each subject
will stay on the dose level at a schedule assigned at trial entry. Subjects can be replaced
for any reason other than a DLT. Subjects will receive treatment for ≤ 2 years or until PD,
unacceptable toxicity, or any criterion for stopping the study drug or withdrawal of trial
occurs.
Inclusion Criteria:
1. Voluntarily agree to participate by giving signed, dated, and written informed consent
prior to any study specific procedures. Participation in pharmacogenomics 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 and bone marrow reserve function, as indicated by the following
laboratory values:
1. Adequate hematological function, defined as absolute neutrophil count ≥ 1.5 × 109
/L, platelet count ≥ 100 × 109 /L, and hemoglobin ≥ 8 g/dL without recent
transfusion (defined as a transfusion that has occurred within 2 weeks of the
hemoglobin measurement).
2. Adequate liver function, defined as total bilirubin level ≤ 1.5 × institutional
upper limit of normal (IULN), aspartate aminotransferase ≤2.5 × IULN, and alanine
aminotransferase ≤ 2.5 × IULN.
3. Adequate renal function defined as creatinine ≤ 1.5 × IULN OR calculated
creatinine clearance ≥ 40 mL/minute per institutional standard. Assessment
methods should be recorded.
4. Adequate coagulation, defined as international normalized ratio or prothrombin
time ≤ 1.5 × IULN and activated partial thromboplastin time ≤ 1.5 × IULN (unless
patient receiving anticoagulant therapy).
7. No history of prior or concomitant malignancy that requires other active treatment.
8. Patients must provide sufficient and adequate formalin-fixed paraffin-embedded tumor
tissue sample (fresh biopsy) collected within 28 days before the first dose from a
site not previously irradiated and to agree to a mandatory on-treatment biopsy if
clinically feasible.
9. Female patients 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:
1. ≥ 45 years of age and has not had menses for > 1 year.
2. Amenorrheic for > 2 years without a hysterectomy and oophorectomy and
follicle-stimulating hormone value in the postmenopausal range upon prestudy
(screening) evaluation.
3. Status is post-hysterectomy, -oophorectomy, or -tubal ligation.
10. Female patients 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 patient.
11. Male patients with a female partner(s) of childbearing potential must agree to use
highly effective contraceptive measures throughout the study 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 patient.
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 study treatment.
2. Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or
major surgery within 3 weeks prior to first dose of study treatment. A 1-week washout
is permitted for palliative radiation to non-central nervous system (CNS) disease,
with Sponsor approval.
3. Patients who have received prior therapy with any anti-CD137 monoclonal antibody or
agent may be enrolled in selected indications upon agreement with the Sponsor.
Note: Selected cohorts may accept prior therapy with an anti-CD137 antibody or agent.
4. Persistent toxicity of National Cancer Institute Common Terminology Criteria for
Adverse Events (NCICTCAE) Grade > 1 severity that is related to prior therapy.
Note: Sensory neuropathy or alopecia of Grade ≤ 2 are acceptable.
5. Expected to require any other form of systemic or localized antineoplastic therapy
while on study (including maintenance therapy with another agent, radiation therapy,
and/or surgical resection).
6. Known severe (Grade ≥ 3) hypersensitivity reactions to fully human monoclonal
antibodies, or severe reaction to immuno-oncology agents, such as colitis or
pneumonitis requiring treatment with steroids; or has a history of interstitial lung
disease, any history of anaphylaxis, or 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 study
treatment or receiving any other form of systemic immunosuppressive medication.
Note: Corticosteroid use as a premedication for IV contrast allergies/reactions is
allowed. Patients 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: Patients 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 study medication.
9. Active or history of autoimmune disease that requires systemic treatment within 2
years of the start of study treatment (i.e. with use of disease-modifying agents,
corticosteroids, or immunosuppressive drugs).
Note: Patients 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 except for corneal
transplantation.
11. Active infection requiring treatment.
12. Known history of HIV type 1 or 2 antibodies.
13. Current or chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus
(HCV) defined as:
- Positive test for hepatitis B surface antigen indicating active or chronic
infection. Note: Patients with previous history of HBV (who have cleared the
infection and have natural immunity, i.e. hepatitis B core antibody positive
cases) are excluded.
- Positive test for (HCV)RNA indicating active or chronic infection. Note: Patients
with positive HCV antibody and negative HCV by polymerase chain reaction 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, any active infections, or
laboratory abnormality that might confound the results of the study, interfere with
the patient's participation for the full duration of the study, or is not in the best
interest of the patient 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 study.
17. Legally incapacitated or has limited legal capacity.
18. Pregnant or breastfeeding.
