| Eligibility |
Inclusion Criteria:
To be eligible for participation in this trial the subject must:
1. Voluntarily agree to participate by giving written informed consent. (Participation in
pharmacogenomics testing is optional.)
2. Be =18 years of age.
3. Diagnosis:
1. Phase 1: Male or female having a histologically or cytologically confirmed
diagnosis of a locally advanced, recurrent, and/or metastatic solid tumor for
which no standard therapy is available or standard therapy has failed.
2. Phase 2:
I. Female having (1) a histologically or cytologically confirmed diagnosis of squamous
cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, and (2)
locally advanced, recurrent, and/or metastatic disease at the time of enrollment.
Histologic confirmation of the original primary tumor is required via pathology
report.
Note: The following cervical tumors are not eligible: minimal deviation/adenoma
malignum, gastric type adenocarcinoma, clear cell carcinoma, and mesonephric
carcinoma.
II. Has cervical cancer and has relapsed after a platinum-based treatment (first line)
regimen for locally advanced, recurrent, and/or metastatic disease; Note: Subjects who
only received platinum-based chemotherapy concurrently with primary radiation (e.g.,
weekly cisplatin) or adjuvant chemotherapy following completion of radiation therapy
(e.g., paclitaxel and carboplatin for =4 cycles) and progressed within 6 months after
treatment completion will be eligible as this systemic therapy will be considered
first line.
4. Measurable Disease:
1. Phase 1: Have objective evidence of disease; the presence of measurable disease
is not required.
2. Phase 2: Have measurable disease on imaging based on RECIST version 1.1. Note:
Subjects must have at least one "target lesion" to be used to assess response, as
defined by RECIST version 1.1. Tumors within a previously irradiated field will
be designated as "non-target" lesions unless progression is documented, or a
biopsy is obtained to confirm persistence at least 90 days following completion
of radiation therapy.
Note: Measurable disease by RECIST 1.1 must be confirmed by independent central
radiologic review prior to first dose. Subjects without centrally confirmed measurable
disease at baseline will not be eligible for this trial.
5. Have a life expectancy of at least 3 months and an Eastern Cooperative Oncology Group
(ECOG) performance status of 0 or 1.
6. Have adequate organ function as indicated by the following laboratory values:
1. Adequate hematological function defined by absolute neutrophil count (ANC) =1.5 x
10^9/L, platelet count =100 x 10^9/L, and hemoglobin
=8 g/dL (without transfusions within 1 week of first dose).
2. Adequate hepatic function based on a total bilirubin level <1.5 x the
institutional upper limit of normal (IULN), aspartate aminotransferase (AST)
level =2.5 x IULN, alanine aminotransferase (ALT) level =2.5 x IULN, and alkaline
phosphatase =2.5 IULN.
3. Adequate renal function defined as creatinine =1.5 x IULN OR calculated
creatinine clearance =50 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).
4. Adequate coagulation defined by international normalized ratio (INR) or
prothrombin time =1.5 x IULN (unless the subject is receiving anticoagulant
therapy); and activated partial thromboplastin time (aPTT) =1.5 x IULN (unless
the subject is receiving anticoagulant therapy)
7. Other than the cancer for which the subject is enrolled, have no history of prior
malignancy, with the exception of basal cell carcinoma of the skin, superficial
bladder cancer, squamous-cell carcinoma of the skin, or has undergone potentially
curative therapy with no evidence of that disease recurrence for 5 years since
initiation of that therapy.
Note: In Phase 2, the history and time requirement for no evidence of disease for 5
years does not apply to the cancer for which the subject is enrolled in the trial.
8. In Phase 2, 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 locally advanced,
recurrent, and/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.
Note: Tissue from needle or excisional biopsy or from resection is required.
9. Female subjects must have a negative serum pregnancy test at screening (within 72
hours of first dose of study drug) if of childbearing potential or be of non-
childbearing potential. Non-childbearing potential is defined as (by other than
medical reasons):
1. =45 years of age and has not had menses for greater than 1 year,
2. Amenorrheic for = 2 years without a hysterectomy and oophorectomy and a
follicle-stimulating hormone (FSH) value in the postmenopausal range upon
pretrial (screening) evaluation,
3. Whose status is post hysterectomy, oophorectomy, or tubal ligation.
10. If of childbearing potential, female subjects must be willing to use 2 highly
effective contraceptive measures (defined in the informed consent form [ICF])
throughout the study, starting with the screening visit through 120 days after the
last dose of study drug.
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 2
highly effective contraceptive measures (defined in the ICF) throughout the trial
starting with the screening visit through 120 days after the last dose of study drug
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
for the subject.
12. Is willing and able to comply with the requirements of the protocol.
Exclusion Criteria
The subject must be excluded from participating in the trial if the subject:
1. Is currently participating and receiving trial therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of treatment.
2. Has an inadequate washout period prior to first dose of study drug defined as:
1. Received systemic cytotoxic chemotherapy or biological therapy within 3 weeks
before first dose,
2. Received radiation therapy within 3 weeks before first dose, or
3. Had major surgery within 4 weeks before first dose.
3. Has received prior therapy with:
1. Any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints)
such as anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4)
antibodies
2. For Phase 2: >1 systemic treatment regimen for the locally advanced recurrent,
and/or metastatic cervical cancer for which the subject is considered for the
study. Subjects who received a systemic regimen immediately after progressing
within 6 months of completing chemotherapy concurrent with primary radiation or
adjuvant chemotherapy after radiation will only be considered as having 1 prior
systemic regimen for the purpose of this criterion.
Note: In Phase 1, prior treatment with a CTLA-4 antibody is permissible for subjects
with metastatic melanoma.
4. Has persisting toxicity related to prior therapy of National Cancer Institute Common
Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE) Grade >1 severity.
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. Has known severe hypersensitivity reactions to fully human monoclonal antibodies
(NCI-CTCAE Version 4.03 Grade =3), any history of anaphylaxis, or uncontrolled asthma.
7. Is receiving systemic corticosteroid therapy =7 days prior to first dose of study
treatment or receiving any other form of systemic immunosuppressive medication
(corticosteroid use on study for management of immune-related adverse events (AE),
and/or a premedication for intravenous (IV) contrast allergies/reactions is allowed).
Subjects who are receiving daily corticosteroid replacement therapy are an exception
to this rule. Examples of permitted therapy are daily prednisone at doses of 5 to 7.5
mg or equivalent hydrocortisone dose, and steroid therapy administered by topical,
intraocular, intranasal, and/or inhalation routes.
8. Has a central nervous system (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 (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, steroids must be discontinued =7 days prior to
first dose of study drug.
9. Has active or history of autoimmune disease that has required systemic treatment
within 2 years of the start of study treatment (i.e. with use of disease modifying
agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (i.e.,
thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or
pituitary insufficiency, etc.) is not considered a form of immunosuppressive systemic
treatment.
Note: Subjects with diabetes type 1, vitiligo, psoriasis, hypo-, or hyperthyroid
disease not requiring immunosuppressive treatment are eligible.
10. Has had an allogeneic tissue/solid organ transplant.
11. Has or had interstitial lung disease (ILD) OR has had a history of pneumonitis that
has required oral or IV corticosteroids.
12. Has an active infection requiring IV systemic therapy.
13. Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
14. Has known active Hepatitis B, Hepatitis C, or tuberculosis. Active Hepatitis B is
defined as a known positive HBsAg result. Active Hepatitis C is defined by a known
positive Hep C Ab result and known quantitative HCV RNA results greater than the lower
limits of detection of the assay.
15. Has 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. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
18. Is, at the time of signing informed consent, a regular user (including "recreational
use") of any illicit drugs or had a recent history (within the last year) of substance
abuse (including alcohol).
19. Is legally incapacitated or has limited legal capacity.
20. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of AGEN2034 and/or AGEN1884.
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