| Eligibility |
Inclusion Criteria
To be eligible for this study, patients must meet the following inclusion criteria:
1. Histologically confirmed AS not amenable to curative intent surgery
2. Prior treatment history for AS
1. Cohort 1 and Cohort 3
- Patients who previously received and progressed after at least 1 prior
therapy for AS.
- Checkpoint inhibitor (PD-1/PD-L1/CTLA-4) naïve
2. Cohort 2
- Patients who previously received and progressed on or after at least 1 prior
therapy for AS
- Prior treatment must include PD-1 or PD-L1 inhibitor such as nivolumab,
pembrolizumab, atezolizumab, durvalumab, AGEN2034, or other, given either as
the most recent treatment or earlier. Note: Confirmation of PD is required
after treatment with prior checkpoint inhibitors
- CTLA-4 inhibitor naïve
3. = 18 years of age.
4. At least one lesion measurable, either radiologically (computed tomography [CT],
magnetic resonance imaging [MRI]) and/or using color photography with a ruler, as per
RECIST v1.1
5. Have a life expectancy of = 3 months and an Eastern Cooperative Oncology Group
Performance Status of 0 to 1
6. Resolution of all acute AEs resulting from prior cancer therapies to National Cancer
Institute Common Terminology Criteria for Adverse Events Version 5.0 Grade = 1
7. Have adequate organ function as indicated by the following laboratory values:
1. Adequate hematological function defined by absolute neutrophil count > 1.5 ×
10^9/L, platelet count > 75 × 10^9/L, and hemoglobin > 8 g/dL (without
transfusions, within
1 week of first dose)
2. Adequate hepatic function based by a total bilirubin level = × 1.5 the upper
limit of normal (ULN), aspartate aminotransferase level = 2.5 × ULN, alanine
aminotransferase level = 2.5 × ULN, alkaline phosphatase = 2.5 × ULN, and albumin
= 3.0 mg/dL
3. Adequate renal function defined as creatinine = 1.5 × ULN OR measured or
calculated creatinine clearance = 40 mL/minute per Institutional standard.
Assessment methods should be recorded
4. Adequate coagulation defined by international normalized ratio or prothrombin
time = 1.5 × ULN (unless the patient is receiving anticoagulant therapy); and
activated partial thromboplastin time = 1.5 × ULN (unless the patient is
receiving anticoagulant therapy)
8. Willing to undergo mandatory fresh tumor biopsy, from a site not previously irradiated
(unless progressed after radiation treatment) Note: Tissue from core, or punch
excisional biopsy, or from resection is required
9. Women of child-bearing potential (WCBP) must have a negative serum pregnancy test at
Screening (within 72 hours prior to first dose of study medication)
Note: 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/or oophorectomy and
follicle-stimulating hormone value in the postmenopausal range upon pre-study
(Screening) evaluation
3. Status is post hysterectomy, oophorectomy, or tubal ligation
10. WCBP must be willing to use highly effective contraception throughout the study,
starting with the Screening Visit through 90 days after the last dose of study
treatment
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
12. Willingness and ability to consent to participate in study and comply with all study
procedures
Exclusion Criteria
To be eligible for this study, patients must not have any of the following exclusion
criteria:
1. Is currently participating and receiving study therapy or has participated in a
different study of an investigational agent and received study therapy or used an
investigation device within 3 weeks of the first dose of treatment
2. Has an inadequate washout period prior to first dose of study drug defined as:
1. < 3 weeks from last dose of prior systemic cytotoxic chemotherapy or biological
therapy
2. < 3 weeks from last radiation therapy
3. < 4 weeks from major surgery
3. Known severe (Grade = 3) hypersensitivity reactions to fully human mAbs, antibody, or
severe reaction to immuno-oncology agents, such as colitis or pneumonitis requiring
treatment with steroids
4. Has received systemic corticosteroid therapy = 7 days prior to the first dose of study
treatment or receiving any other form of systemic immunosuppressive medication
(corticosteroid use on study for management of immune-related AEs, and/or a
premedication for intravenous (IV) contrast allergies/reactions is allowed). Patients
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
5. Known central nervous system 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 (based on 2 sets of brain images, performed = 4
weeks apart, and obtained after the brain metastases treatment).
In addition, any neurologic symptoms that developed either as a result of the brain
metastases or their treatment must have resolved or be minimal and be expected as
sequelae from treated lesions. For individuals who received steroids as part of brain
metastases treatment, high-dose steroids must be discontinued = 7 days prior to first
dose of study drug but may be continued if = 5 mg/day (prednisone)
6. Has active or history of autoimmune disease requiring immunosuppressive systemic
treatment (e.g. modifying agents, corticosteroids or immunosuppressive drugs) within
previous 2 years Note: Thyroxine, insulin, or physiologic corticosteroid replacement
therapy for adrenal or pituitary insufficiency is not considered a form of
immunosuppressive systemic treatment.
Note: Patients with Type 1 diabetes, vitiligo, psoriasis, hypo-, or hyperthyroid
disease not requiring immunosuppressive treatment are eligible
7. Has had an allogeneic tissue/solid organ transplant
8. Has or had interstitial lung disease or has had a history of pneumonitis anaphylaxis,
or uncontrolled asthma that has required oral or IV corticosteroids
9. Active infection requiring IV systemic therapy
10. Known history of HIV type 1 or 2 antibodies
11. Known active infection with hepatitis B and/or hepatitis C virus
12. History of seizure disorders
13. Clinically significant 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
14. History or current evidence of any condition, therapy, 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
15. Psychiatric or substance abuse disorder that would interfere with cooperation with the
requirements of the study
16. Legally incapacitated or has limited legal capacity
17. Pregnant or breastfeeding
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