| Eligibility |
Inclusion Criteria:
- 1.Subject is willing and able to provide signed and dated informed consent prior to
all study-related procedures and is able to comply with all study procedures;
- 2.Patients with histologically or cytologically confirmed solid tumors who have failed
standard of care or have no standard of care;
- 3.Male or female, aged = 18 years;
- 4.Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1;
- 5.Have life expectancy of at least 12 weeks based on investigator's judgement;
- 6.Subjects must meet the following laboratory values at the screening visit:
a)Absolute neutrophil count (ANC) =1.5 x 109/L (in absence of growth factor or other
support within 2 weeks prior to study entry) ; Platelet count =100 x 109/L;Hemoglobin
=9 g/dL or = 5.6 mmol/L (without growth factor and transfusion support within 14 days
prior to study entry . b)Serum creatinine < 1.5 × ULN, calculated creatinine clearance
(CrCL) > 50 mL/min (Cockroft-Gault formula) or estimated glomerular filtration rate
(GFR) > 50 mL/min; c)Aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) and alkaline phosphatase =3.0 x ULN; AST or ALT = 5 × ULN if liver metastases
are present; d) Serum total bilirubin (TBIL) = 1.5 ULN (for patients with Gilbert's
syndrome, TBIL = 3 × ULN); e)International normalized ratio (INR) = 2.0 and activated
partial thromboplastin time (aPTT) = 1.5 × ULN. Exception: INR 2 to = 3 is acceptable
for subjects on Warfarin anticoagulation.
- 7.Women of reproductive potential who are sexually active with a non-sterilized male
must consistently use highly effective contraception/birth control between signing of
the informed consent and 120 days after the last administration of the study drug.
Exclusion Criteria:
- 1.Previous exposure to TNFR such as anti-CD137, OX40, CD27 and CD357 antibodies.
- 2.Patients with any other malignancy within the past 5 years or currently, except for
completely cured non-melanoma skin cancer, carcinoma in situ of the cervix, and ductal
carcinoma in situ of the breast;
- 3.Patients with hematological malignancies (such as acute lymphoblastic leukemia,
acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma, chronic
myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, etc.);
- 4.Subjects have received any anticancer therapy or another investigational agent
within the shorter of 4 weeks or 5 half-lives before the first dose of the study
treatment.Subjects have received Modern traditional Chinese medicine preparations with
anti-tumor effect approved by NMPA = 2 weeks prior to first medication.Prior
palliative radiotherapy to bone metastases = 2 weeks prior to the first dose of study
treatment is acceptable.
- 5.Continuance of toxicities due to prior radiotherapy or chemotherapy agents that have
not recovered to = Grade 1 per CTCAE 5.0, except alopecia,= Grade 2 sensory
neuropathy,lymphopenia, endocrine disease controlled by hormone replacement therapy;.
- 6.Subjects with a history of = Grade 3 immune-related adverse events resulted from
previous immunotherapy or treatment discontinuation due to previous
immunotherapy.Except hypothyroidism, type 1 diabetes and dermatitis (excluding Steven
Johnson syndrome and toxic epidermal necrolysis);
- 7.History of clinically significant sensitivity or allergy to monoclonal antibodies
and their excipients or known allergies to antibodies produced from Chinese hamster
ovary cells
- 8.Primary central nervous system (CNS) malignancies or symptomatic CNS
metastases,except for the following. a) Subjects with asymptomatic brain metastases
(No progressive central nervous system symptoms caused by brain metastases, no need
for corticosteroids, and lesion size = 1.5 cm);b)Subjects with stable lesions
confirmed by imaging examination after local treatment of brain metastases for = 4
weeks, and who discontinued glucocorticoid or anticonvulsant drug treatment 2 weeks
before administration of the study drug;
- 9.History of non-infectious pneumonitis or interstitial lung disease that required
corticosteroids treatment , except for those caused by radiotherapy, or current
interstitial pneumonitis or pneumonitis; or history of other serious lung diseases;
- 10.History of active autoimmune disease, autoimmune disease requiring systemic
treatment, or history of autoimmune disease within 2 years prior to the first dose.
Exceptions are the following: vitiligo, childhood asthma/idiosyncratic reactions, etc.
for which alternative treatments are available;
- 11.Clinically uncontrolled intercurrent illness, including but not limit to
uncontrolled diabetes (blood glucose > 250 mg/dl,1 mg/dl=18 mmol/L),uncontrolled
hypertension(Systolic blood pressure > 150 mmHg or/and diastolic blood pressure > 100
mmHg),History of hypertension or hypertensive encephalopathy; severe thyroid
dysfunction and other serious endocrine diseases or other serious diseases requiring
systemic treatment; active infection (such as active pulmonary tuberculosis); active
coagulation disorders; other serious diseases requiring systemic treatment;
- 12.Severe cardiovascular disease including symptomatic congestive heart failure (New
York Heart Association class III or IV), unstable angina,cardiac arrhythmia, a history
of myocardial infarction within 6 months or a history of arterial thromboembolic event
and pulmonary embolism within 3 months of the first dose of investigational agent.
- 13.QTc > 470 ms at baseline; Concomitant medications that would prolong the QT
interval; Family history of long QT syndrome.
- 14.Subjects must not have active infection of human immunodeficiency virus, hepatitis
B, or hepatitis C
- 15. Subjects must not receive concurrent or prior use of an immunosuppressive agent
within 4 weeks of the first dose of YH003, with the following exceptions and
notes:a)Systemic steroids at physiologic doses (equivalent to dose of oral prednisone
10 mg) are permitted. b)Intranasal, inhaled, topical, intra-articular, and ocular
corticosteroids with minimal systemic absorption are permitted.
- 16.Major surgery within 4 weeks prior to study entry and Minor surgery within 2 weeks
prior to the first dose of YH003.
- 17.Subjects must not have received a live attenuated vaccine within 28 days before the
first dose of YH003, and subjects, if enrolled, should not receive live vaccines
during the study or for 180 days after the last dose of YH003.
- 18.Subjects who have had an allogeneic bone marrow transplant or organ transplant.
- 19.Subjects with psychiatric disorder, history of drug abuse, history of drug abuse,
or history of alcohol dependence that may affect trial compliance
|
