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 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
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.
