| Eligibility |
Inclusion Criteria:
1. Voluntarily agree to participate by giving signed, dated, and written informed consent
prior to any study-specific procedures (participation in genetic testing is optional).
2. Histologically confirmed diagnosis of a solid tumor that is currently metastatic or
locally advanced for which no standard therapy is available or standard therapy has
failed.
3. Measurable disease on baseline imaging based on RECIST 1.1.
4. Life expectancy of at least 3 months.
5. Eastern Cooperative Oncology Group 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 ×
10^9/liter (L), platelet count = 100 × 10^9/L, and hemoglobin = 8 grams
(g)/deciliter (dL) without recent transfusion (defined as a transfusion that has
occurred within 2 weeks of the hemoglobin measurement).
2. Adequate liver function, defined as serum albumin = 3.0 g/dL, total bilirubin
level = 1.5 × institutional upper limit of normal (IULN), aspartate
aminotransferase = 2.5 × IULN, and alanine aminotransferase = 2.5 × IULN, and
alkaline phosphatase = 2.5 × IULN or = 5 × IULN for participants with liver
metastases.
3. Adequate renal function defined as calculated creatinine clearance = 40
milliliters/minute as assessed by Cockcroft-Gault method.
4. Adequate coagulation, defined as international normalized ratio or prothrombin
time = 1.5 × IULN and activated partial thromboplastin time = 1.5 × IULN (unless
participant is receiving anticoagulant therapy).
7. Participants with a history of prior malignancy are eligible if treatment was
completed = 2 years prior to the first dose of study treatment and the participant has
no evidence of disease. Participants who have been maintained on stable doses of
antineoplastic hormonal therapy within that 2-year time frame may also be eligible
with approval of the Medical Monitor. Participants with a history of prior early-stage
basal/squamous cell skin cancer, or noninvasive or in situ cancers, who have undergone
definitive treatment at any time are also eligible.
8. Participants must provide a sufficient and adequate formalin-fixed paraffin embedded
tumor tissue sample (biopsy) collected after the last dose of prior anti-cancer
therapy and before the first dose of study treatment from a site not previously
irradiated and agree to a mandatory on-treatment biopsy, if clinically feasible. If a
potential study participant cannot provide a tumor tissue sample as specified above,
enrollment may be possible following discussion and approval from the Medical Monitor.
9. Female participants of childbearing potential must have a negative urine or serum
pregnancy test at screening (within 72 hours of first dose of study medication) with
repeat urine or serum pregnancy test on Day 1 of each cycle and at the End of
Treatment visit. If a urine pregnancy test is positive, results must be confirmed with
a serum pregnancy test. Non-childbearing potential is defined as follows:
1. = 50 years of age and has not had menses for greater than 1 year.
2. Amenorrheic for = 2 years without a hysterectomy and bilateral oophorectomy and a
follicle-stimulating hormone value in the postmenopausal range upon pre-study
(screening) evaluation.
3. Status is post hysterectomy, bilateral oophorectomy, or tubal ligation.
Female participants who are diagnosed with a tumor that is known to secrete human
chorionic gonadotropin must be certified not pregnant based on clinical evidence and
investigator judgment.
Female participants of child-bearing potential must agree to use highly effective
contraceptive measures starting with the screening visit through 90 days after the
last dose of study treatment.
Note: Abstinence is acceptable if this is the established and preferred contraception
for the participant.
10. Male participants 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
for the participant.
11. 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 investigational device
within 3 weeks of first dose of current study drug.
2. Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or
major surgery outside of the acceptable washout periods prior to first dose of study
drug. The following washout windows are acceptable from prior treatments, that is
participants with time periods less than the following should be excluded:
1. Cytotoxic agent or monoclonal antibody = 3 weeks is acceptable (that is, < 3
weeks should be excluded).
2. A 1-week washout is permitted for palliative radiation to non-central nervous
system (CNS) disease.
3. Small molecule targeted investigational therapies and tyrosine kinase inhibitors
= 14 days or 5 half-lives is acceptable (that is, < 14 days or < 5 half-lives
should be excluded).
4. Having a previous severe acute respiratory syndrome coronavirus 2 vaccine > 7
days before administration is acceptable. For vaccines requiring more than 1
dose, the full series should be completed prior to Cycle 1 Day 1 (C1D1), when
feasible, and when the delay in initiation of study treatment would not put the
study participants at risk.
5. Prior radiation therapy to the CNS within 2 weeks before first treatment.
3. Persistent toxicity of National Cancer Institute Common Terminology Criteria for
Adverse Events Version 5.0 Grade >1 severity that is related to prior therapy.
a. Sensory neuropathy or alopecia of Grade = 2 is acceptable. Stable, compensated
endocrinopathies (hypothyroidism, adrenal insufficiency, hypophysitis) that are the
sequelae of immune-mediated adverse events > Grade 1 are acceptable.
4. Known severe (Grade = 3) hypersensitivity reactions to fully human monoclonal
antibodies, or to any study drug excipients, or severe reaction to immuno-oncology
agents, such as colitis or pneumonitis requiring treatment with steroids; or has a
history of or active interstitial lung disease, any history of anaphylaxis, or
uncontrolled asthma.
5. Participants with a condition requiring systemic treatment with either corticosteroids
(> 10 milligrams [mg] daily prednisone equivalent) within 14 days or any other
immunosuppressive medication within 30 days of the first dose of study treatment.
Inhaled or topical steroids, and adrenal replacement steroid doses (= 10 mg daily
prednisone equivalent), are permitted in the absence of active autoimmune disease.
6. Active CNS metastases. Note: Participants are eligible if CNS metastases have been
treated and participants are radiologically and clinically stable. Participants must
have been either off corticosteroids, or on a stable or decreasing dose of = 10 mg
daily prednisone or equivalent for at least 2 weeks prior to the first dose of study
treatment.
7. Active or history of autoimmune disease that requires systemic treatment within 2
years of the start of study drug (that is, with use of disease-modifying agents,
corticosteroids, or immunosuppressive drugs). Note: Participants with autoimmune
conditions requiring hormone replacement therapy or topical treatments are eligible.
8. Participants has had an allogeneic tissue/solid organ transplant, except for corneal
transplants.
9. An active infection requiring treatment within 2 weeks of C1D1, or active interstitial
lung disease.
10. Human immunodeficiency virus (HIV) positive:
1. Participants with cluster of differentiation 4 > 200 cells/cubic millimeter are
eligible.
2. Participants with undetectable HIV viral load are eligible.
11. Active hepatitis B (HBV) or active hepatitis C (HCV).
1. Participants with HBV infection are eligible if HBV surface antigen and HBV DNA
are negative.
2. Participants with HCV infection are eligible if HCV RNA is negative.
12. Clinically significant (that is, 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.
13. History or current evidence of any condition (including psychiatric or substance abuse
disorder that would interfere with the requirements of the trial), therapy, any active
infection requiring treatment within 2 weeks of C1D1, or laboratory abnormality that
might confound the results of the trial, interfere with the participant's
participation for the full duration of the trial, or is not in the best interest of
the participant to participate, in the opinion of the treating Investigator.
14. Legally incapacitated or has limited legal capacity.
15. Pregnant or breastfeeding.
16. Corrected QT interval (QTc) > 480 milliseconds at screening except if the prolonged
QTc is due to right bundle branch block.
17. Uncontrolled hypertension or controlled hypertension (> 140/90 millimeters of mercury)
on more than 3 antihypertensive agents.
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