| Eligibility |
Inclusion Criteria:
1. Has provided written informed consent
2. Age = 18 years.
3. In dose-escalation cohorts (Phase 1a), subjects must have histologically or
cytologically confirmed advanced or metastatic solid tumor that is refractory or
relapsed to the current standard therapies, or for which no effective standard therapy
is available, or whereby standard therapy has been refused.
4. In pharmacodynamic-confirmation cohorts (Phase 1a), additional enrolled subjects must
have histologically or cytologically confirmed selected advanced or metastatic solid
tumors, refractory or relapsed to the current standard therapies, or for which no
effective standard therapy is available. Other tumor types can be considered after
discussion with the Sponsor.
5. In dose-expansion cohorts (Phase 1b), subjects with specific tumor types will be
enrolled. Subjects must have received no more than three prior lines of systemic
therapy (including approved and investigational treatments) for advanced or metastatic
disease. Other cohorts of different tumor types may be added based on the emerging
pharmacodynamic and anti-tumor response data.
6. Subjects must have measurable lesions according to RECIST v1.1. A previously
irradiated lesion can be considered a target lesion if the lesion is measurable per
RECIST v1.1, and there is objective evidence of interval increase in size since
radiotherapy.
7. For dose-escalation cohorts (Phase 1a), subjects must have available archived tumor
tissue sample (block or a minimum of 10 unstained slides of formalin-fixed
paraffin-embedded [FFPE] tissues) to allow for correlative biomarker studies.
8. For pharmacodynamic-confirmation cohorts (Phase 1a) and dose-expansion cohorts (Phase
1b), subjects must be willing to provide 2 fresh biopsy samples (pre-treatment and on
treatment), where clinically appropriate.
9. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to1.
10. Adequate organ function
11. Life expectancy =12 weeks;
12. Females of childbearing potential must be willing to use a highly effective method of
birth control for the duration of the study, and within 120 days after the last dose
of investigational product.
13. Non-sterile males must be willing to use a highly effective method of birth control
for the duration of the study and within 120 days after the last dose of
investigational product.
Exclusion Criteria:
1. Receipt of the following treatments or procedures:
1. Anticancer small-molecule targeted agent (e.g., tyrosine kinase inhibitor) within
2 weeks prior to the first dose of investigational product;
2. Anti-PD-1/PD-L1 mAb within 4 weeks prior to the first dose of investigational
product;
3. Prior use of approved or investigational anti-CTLA-4 therapy, anti-CD73 therapy
or adenosine 2A receptor inhibitors, or any other antibody or drug targeting T
cell costimulation or immune checkpoint pathways such as ICOS, or agonists such
as CD40, CD137, GITR, OX40 etc.
4. Other anticancer mAb within 4 weeks or 5 half-lives (whichever is less) prior to
the first dose of investigational product;
5. Other anticancer therapy (e.g., chemotherapy, radiotherapy, etc.) within 4 weeks
prior to the first dose of investigational product; [Note: Palliative
radiotherapy > 1 week prior to first dose is allowed]
6. Any major surgery (e.g., laparotomy, thoracotomy, removal of organ[s]) within 4
weeks prior to the first dose of investigational product;
7. Any other non-approved investigational product or procedure within 4 weeks prior
to the first dose of investigational product, or concurrent participation in
another therapeutic clinical study;
2. Any condition that required systemic treatment with corticosteroids (> 10 mg daily
prednisone or equivalent) or other immunosuppressive agents within 14 days prior to
the first dose of investigational product.
3. Receipt of live attenuated vaccines within 4 weeks prior to the first dose of
investigational product; Note: seasonal vaccine for influenza which is generally
inactivated is allowed.
4. Prior organ transplantation;
5. Prior malignancy active within the previous 3 years except for the tumor for which a
subject is enrolled in the study, and locally curable cancers that have been
apparently cured, such as basal cell cancer or carcinoma in situ of the cervix or
breast;
6. 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).
7. Active infections (including tuberculosis) requiring systemic antibacterial,
antifungal, or antiviral therapy within 14 days prior to the first dose of
investigational products. Note: antiviral therapy is permitted for patients with viral
hepatitis;
8. Known history of human immunodeficiency virus (HIV) infection;
9. Known active hepatitis B or C infections (Active hepatitis B is defined as a known
positive Hepatitis B surface antigen [HBsAg] result. Active hepatitis C is defined by
a known positive Hepatitis C virus [HCV] antibody with detectable HCV ribonucleic acid
[RNA] results);
10. Active autoimmune diseases or history of autoimmune diseases that may relapse. Note:
Subjects with controlled type 1 diabetes mellitus, thyroiditis in euthyroid state or
hypothyroidism well managed by hormone replacement therapy (HRT), or skin diseases not
requiring systemic treatment (e.g., vitiligo, psoriasis) are eligible;
11. History of interstitial lung disease, noninfectious pneumonitis except for those
induced by radiation therapies;
12. Uncontrolled massive ascites or pleural effusion, as determined by the Investigator;
13. Patients with clinically significant cardio-cerebrovascular or venous thromboembolic
disease.
14. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) = 470 msec
calculated from 3 ECGs (within 5 minutes at least 1 minute apart);
15. Uncontrolled intercurrent illness including, but not limited to, uncontrolled
hypertension, uncontrolled diabetes, uncontrolled endocrinopathy, severe active peptic
ulcer disease or gastritis, or psychiatric illness/social situations that would limit
compliance with study requirement or compromise the ability of the subject to give
written informed consent;
16. History of severe hypersensitivity reactions to other mAbs;
17. Toxicities of prior anticancer therapy have not resolved to NCI-CTCAE version 5.0
Grade =1, or to levels dictated in the inclusion/exclusion criteria, except toxicities
not considered a safety risk (e.g., alopecia, neuropathy, or asymptomatic laboratory
abnormalities);
18. Pregnant or breastfeeding women;
19. Any other conditions that, in the opinion of the Investigator, would interfere with
evaluation of the investigational product or interpretation of subject safety or study
results.
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