| Eligibility |
Inclusion Criteria:
1. Male or female =18 years of age at the time of signing informed consent.
2. Diagnosis of histological or cytological confirmed locally advanced, recurrent and/or
metastatic solid tumors that failed to respond to standard therapy,
intolerant/refractory to currently available local therapies, or for whom no
appropriate therapies are available (based on the judgement of the Investigator).
3. Measurable or non-measurable disease according to RECIST 1.1 in dose escalation stage
and at least one measurable lesion is necessary for dose expansion stage.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, and
anticipated life expectancy of = 3 months.
5. Adequate hematologic function based on the following (with no blood transfusion or
hematopoietic stimulating factor therapy within 14 days prior to study drug
administration):
1. ANC=1.2 ×10^9/L
2. Platelet count =75×10^9/L
3. Hemoglobin =8.0 g/dL
6. Adequate coagulation parameters based on the following:
1. Prothrombin Time-International Normalized Ratio (PT-INR) =1.5×ULN (upper limit of
normal), unless coumarin derivatives are used.
2. Activated partial thromboplastin time (aPTT) =1.5×ULN. Subjects on anticoagulants
may have coagulation parameters that exceed the criteria defined above.
7. Adequate hepatic function based on the following:
1. Total bilirubin (TBIL) =1.5 × ULN and/or isolated elevations of indirect
bilirubin are eligible for study participation.
2. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =3 × ULN (=5 ×
ULN for subjects with known hepatic metastases).
8. Adequate renal function based on serum creatinine clearance =30 mL/min (normal to
moderate renal impairment) as determined by Cockcroft-Gault equation.
9. A female patient is eligible to participate if she is not pregnant or breastfeeding,
and
- is not a WOCBP or
- A WOCBP must have a negative pregnancy test within 72 hours before the first dose
of study drug administration, and additional pregnancy testing during and after
study drug as defined in the SOA .
- A WOCBP must consent to use highly effective contraceptive methods or abstain
from heterosexual activity from screening through 120 days following the last
dose of study treatment.
10. Fertile male subjects, defined as all males physiologically capable of conceiving
offspring, with their WOCBP partner(s) must agree to use highly effective
contraception. Sexually active males who have not had a vasectomy, and whose partner
is reproductively capable, must agree to abstain from sexual intercourse or use
barrier contraception from Screening through 120 days following the last dose of study
treatment.
11. Ability to understand and give written informed consent for participation in this
trial, including all evaluations and procedures as specified by this protocol.
Exclusion Criteria:
1. Inadequate recovery from any prior surgical procedure, or patients having undergone
any major surgical procedure within 4 weeks prior to first administration of study
drug.
2. Has had a known or suspected hypersensitivity reaction to treatment with a mAb and/or
the excipients of NB002.
3. Prior treatment with other TIM-3 inhibitors (e.g., mAbs).
4. Prior palliative radiotherapy within 1 week of start of study treatment. Subjects must
have recovered (CTCAE Grade =1) from all radiation-related toxicities.
5. Any antitumor agent for the primary malignancy without delayed toxicity within 4 weeks
or 5 half-lives, whichever is shorter, prior to first administration of study drug,
except for Nitrosoureas and mitomycin C within 6 weeks prior to first administration
of study drug and during study.
6. Active CNS metastases, however, subjects who have undergone definitive radiation
and/or surgery for the treatment of CNS metastases, who are stable by radiographic and
clinical (neurological) assessment (performed within 4 weeks prior to first trial drug
administration), and who are no longer taking pharmacologic doses of corticosteroids
are eligible; subjects with leptomeningeal metastases or primary CNS malignancies
(such as glioma, glioblastoma) are not eligible.
7. Evidence of metastatic ileus on computed tomography (CT) scan.
8. Patients with concurrent hematologic malignancies.
9. Known active or prior infection with human immunodeficiency virus (HIV), or active
infection with hepatitis B virus (HBV), or hepatitis C virus (HCV).
10. Any other serious/active/uncontrolled infection, any infection requiring parenteral
antibiotics, or unexplained fever > 38ºC within 2 weeks prior to first administration
of study drug.
11. Patients with an active, known or suspected autoimmune disease, or a documented
history of autoimmune disease or syndrome, requiring systemic steroids or other
immunosuppressive medications. procedure is allowed if all other inclusion/exclusion
criteria are met.
12. History of organ transplantation (e.g., stem cell or solid organ transplant)
13. A significant pulmonary disease or condition.
14. Patients with a current or recent (within 6 months) significant gastrointestinal (GI)
disease or condition.
15. History of immune-related toxicity during prior treatment with an immune checkpoint
inhibitor (ICI, e.g., PD-1/PD-L1 or CTLA-4 inhibitor), including any grade =3, and
neurologic and/or ocular immune-related toxicity, pneumonitis, or cardiomyopathy of
any grade that necessitated permanent discontinuation of that therapy. Patients with
other Grade 1-2 immune-related toxicities on prior ICI therapy that have resolved are
NOT excluded. Endocrine immune-related toxicities of grade <3 are allowed, as long as
they are controlled and/or asymptomatic. Substitution therapy following an
immune-related endocrinopathy is allowed.
16. Unresolved > Grade 1 toxicity associated with any prior antitumor therapy except for
persistent Grade 2 alopecia, peripheral neuropathy, decreased hemoglobin, lymphopenia,
hypomagnesemia, and/or end-organ failure being adequately managed by hormone
replacement therapy:
17. Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism
(PE) within 4 weeks prior to first administration of study drug unless adequately
treated and considered by the Investigator to be stable. Active uncontrolled bleeding
or a known bleeding diathesis.
18. Vaccination with live vaccine(s) within 1 month prior to administration.
19. Baseline QT interval corrected with Fridericia's method (QTcF) >470 ms (average of
triplicate electrocardiograms [ECG]).
20. Unstable or severe uncontrolled medical condition (e.g., uncontrolled diabetes),
psychiatric illness/social situations, or any important medical illness or abnormal
laboratory finding that would, in the Investigator's judgment, increase the risk to
the patient associated with his or her participation in the study.
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