| Eligibility |
Inclusion Criteria:
1. Voluntarily signed informed consent form (ICF).
2. Ability and willingness to adhere to all study procedures.
3. Male or female patients = 18 years of age at the time of signing the ICF.
4. Locally advanced unresectable or metastatic solid tumor confirmed by histology or
cytology
5. For Part A: On tumor imaging, as assessed by RECIST v1.1 and iRECIST, with measurable
or unmeasurable disease. For Part B: On tumor imaging, as assessed by RECIST v1.1 and
iRECIST, with at least one measurable disease.
6. Life expectancy = 3 months.
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1 for Part A and
Part B.
8. Adequate end-organ and hematopoietic function, defined based on the following
laboratory results obtained within 7 days prior to the first dose of study treatment
[Day 1]):
1. Absolute neutrophil count (ANC) = 1.5×109/L (1500/µL), without granulocyte
colony-stimulating factor (G-CSF) support. Note that G-CSF may be administered
until 14 days prior to Cycle 1 Day 1 (C1D1).
2. Platelet count = 90×109/L (90,000/µL) without transfusion within 14 days prior to
C1D1.
3. Hemoglobin = 90 g/L (9 g/dL). Note that patients may be transfused or receive
erythropoietic treatment to meet this criterion until 14 days prior to C1D1.
4. Creatinine clearance = 60 mL/min.
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 x the
upper limit of normal (ULN) with or without primary or metastatic liver tumor
lesions.
6. Total bilirubin (TBIL) = 1.5 x ULN.
7. For patients not receiving therapeutic anticoagulation: International Normalized
Ratio (INR), activated partial thromboplastin time (aPTT) and prothrombin time
(PT) = 1.5 x ULN.
8. For patients receiving warfarin: INR = 3.0 x ULN and no bleeding within 14 days
prior to Day 1. Patients receiving therapeutic anticoagulation must be on a
stable dose for a minimum of 14 days prior to Day 1. Patients on low molecular
weight heparin will be allowed.
Exclusion Criteria:
1. Patients with leptomeningeal (LMD) metastases or patients with new and/or progressive
brain metastases at the time of study entry. Patients with treated brain metastases
are eligible if there is no evidence of progression for at least 4 weeks after central
nervous system (CNS)-directed treatment (radiotherapy and/or surgery), as ascertained
by clinical examination and brain imaging (MRI or CT) during the screening period.
2. History of primary malignancy other than the diseases under study, not in remission
greater than three (3) years prior to Day 1. Exceptions that do not require a 3-year
remission include: adequately treated non-melanoma skin cancer, cervical carcinoma in
situ on biopsy or squamous intraepithelial lesion on Papanicolaou (PAP) smear, in situ
prostate cancer (with no evidence of active disease for two [2] years prior to Day 1),
or resected melanoma in situ and radically resected papillary thyroid carcinoma.
3. Persistence of Adverse Events (AEs) from prior anti-cancer therapy that have not
resolved to Grade 1 (except for alopecia and hypothyroidism), or any history of Grade
= 3 immune-related adverse events (irAEs), Grade = 2 pneumonitis, hypophysitis or
encephalitis related to immunotherapy, or other Grade = 3 drug-related CNS toxicity.
4. Active systemic autoimmune disease or a history of autoimmune disorder that may
relapse (e.g., systemic lupus erythematosus [SLE], rheumatoid arthritis, inflammatory
bowel disease [IBD], autoimmune thyroid disorder*, multiple sclerosis, vasculitis,
glomerulitis, eczema, psoriasis, etc.).
*Note that primary or secondary hypothyroidism, well controlled with hormone
replacement therapy is permitted.
5. Major trauma or major surgery within 4 weeks prior to Day 1 or anticipated major
surgery during study participation.
6. Serious unhealing wound, ulcer, or bone fracture.
7. History of and/or presence of any of the following cardiovascular and cerebrovascular
events or conditions:
1. History of myocardial infarction, unstable or severe angina, or arterial
thrombotic event (such as cerebrovascular attack [CVA] or transient ischemic
attack [TIA]) within 12 months prior to Day 1.
2. Significant abnormalities on the screening of ECG, including corrected QT
interval (QTc interval) > 470 msec (average of triplicate measurements,
corrected for heart rate using Fridericia's formula), second degree (Mobitz type
II) or third degree atrioventricular (AV) block, or other clinically significant
(in the Investigator's opinion) arrhythmia.
3. Current New York Heart Association (NYHA) stage II-IV congestive heart failure
(CHF).
4. Left ventricular ejection fraction (LVEF) < 50%.
• Note that LVEF assessment by echocardiogram (ECHO) scan performed as part of
the patient's regular care within 4 weeks prior to the screening visit may be
used for confirmation of eligibility.
5. Other clinically significant (in the Investigator's opinion) cardiac diseases
(e.g., valvular disease, cardiomegaly, ventricular hypertrophy, cardiomyopathy,
myocarditis, etc.).
6. Uncontrolled hypertension (defined as a systolic blood pressure [SBP] = 150 mmHg
and/or diastolic blood pressure (DBP) = 100 mmHg at screening), despite
appropriate antihypertensive therapy, or poor compliance with an antihypertensive
regimen.
8. Active or recent (past 6 months) bleeding disorder, including gastrointestinal (GI)
bleeding, as evidenced by hematemesis, significant hemoptysis, or melena within 6
months prior to Day 1.
9. Uncontrolled diabetes.
10. Chronic severe liver disease or Child-Pugh B or C liver cirrhosis.
11. History of alcoholism or drug abuse within the past year.
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