| Eligibility |
Inclusion Criteria:
1. Males or females of 18 years of age or older (or per local regulations).
2. Have histologically-proven measurable, or evaluable advanced (systemically or locally
progressive), or metastatic solid tumors or the locally advanced disease is not
amenable to local therapy, who have failed, or are intolerant to standard therapy or
for whom no standard therapy is available. (For patients with hepatocellular
carcinoma, the diagnosis needs to be supported by dynamic computed tomography
[CT]/magnetic resonance imaging, if pathological confirmation is not attainable).
3. Eastern Cooperative Oncology Group (ECOG) performance status of = 2 at the time of
study entry.
4. Able to comprehend and provide informed consent.
5. A life expectancy longer than 3 months in the opinion of the Investigator.
6. Adequate hematologic functions, as defined by: absolute neutrophil counts
= 1500/mm3; a hemoglobin level = 10 g/dL; a platelet count = 100,000/mm3.
7. Adequate hepatic function defined by: a total bilirubin level = 1.5 × of upper limit
of normal (ULN); aspartate transaminase and alanine transaminase levels = 2.5 × ULN or
= 5 × ULN in known hepatic metastases or with primary hepatocellular carcinoma.
8. Adequate renal function, as defined by the creatinine clearance = 50 mL/minute (as
calculated by the Cockcroft-Gault formula).
9. Adequate cardiac function defined as left ventricular ejection fraction = 50% by
cardiac ultrasound or multigated acquisition (MUGA) scan. A recent MUGA scan is
acceptable if performed within 8 weeks of the first infusion of IP.
10. Females of child-bearing potential must have a negative pregnancy test upon entry into
this study and must be willing to use highly effective birth control upon enrollment,
during the Treatment Phase and for 180 days following the last dose of study drug. A
female is considered of child-bearing potential following menarche and until becoming
postmenopausal (no menstrual period for a minimum of 12 months) unless permanently
sterile (undergone a hysterectomy, bilateral salpingectomy, or bilateral
oophorectomy).
11. If male, must be surgically sterile or willing to use highly effective birth control
upon enrollment, during the Treatment Phase, and for 180 days following the last dose
of study drug.
12. History of prior major surgery, prior cytotoxic chemotherapy, or prior therapy with
investigational agents, medical device, or local radiotherapy should be at least 28
days prior to Screening and at least 42 days from the last infusion of immune check
point inhibitors (including anti-programmed cell death receptor-1 [PD-1] or
anti-PD-L1) before the first infusion of IP.
13. Child-Pugh score of A (patients with hepatocellular carcinoma only).
14. Able to be followed up as required by the study protocol.
Exclusion Criteria:
1. Persistent = Grade 2 toxicities from prior therapies, with the exception of alopecia
of any grade, Grade = 2 peripheral neuropathy, and laboratory values listed per the
inclusion criteria.
2. Concurrent unstable or uncontrolled medical conditions, including:
- Active systemic infections;
- Poorly controlled hypertension (systolic blood pressure = 160 mmHg or diastolic
blood pressure = 100 mmHg), or poor compliance with antihypertensive agents;
- Clinically significant arrhythmia, unstable angina pectoris, congestive heart
failure (Class III or IV of New York Heart Association) or acute myocardial
infarction within 6 months;
- Uncontrolled diabetes or poor compliance with hypoglycemic agents;
- The presence of chronically unhealed wound or ulcers;
- Other chronic diseases, which, in the opinion of the Investigator, could
compromise safety of the patient or the integrity of the study.
3. Newly-diagnosed or symptomatic brain metastases (patients with a history of brain
metastases must have received definitive surgery or radiotherapy, be clinically
stable, and not be taking steroids for brain edema). Anticonvulsants are allowed.
Patients with history of leptomeningeal disease will be excluded.
4. Any concurrent malignancy other than basal cell carcinoma or carcinoma in situ of the
cervix. (Patients with a previous malignancy but without evidence of disease for = 3
years are allowed to participate).
5. Females who are pregnant, lactating, or intend to become pregnant during their
participation in this study.
6. Known history of human immunodeficiency virus infection.
7. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease, diverticulitis with the exception of diverticulosis,
celiac disease, irritable bowel disease, Wegner syndrome) within the past 2 years.
Patients with well controlled vitiligo, alopecia, and Grave's disease, hypothyroidism
(eg, following Hashimoto syndrome) stable on hormone replacement, or psoriasis not
requiring systemic treatment (within the past 3 years), or patients with controlled
Type 1 diabetes mellitus who are on a stable insulin regimen are not excluded.
8. Current or prior use of immunosuppressive medication within 14 days before the first
dose. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids or local steroid injections (eg,
intra-articular injection), OR
- systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or equivalent, OR
- steroids as premedication for hypersensitivity reactions (eg, CT scan
premedication).
9. History of primary immunodeficiency or allogeneic transplantation.
10. Active hepatitis B (HBsAg reactive). Active hepatitis C virus (HCV) infection, defined
as having a positive HCV antibody test followed by a positive HCV RNA test at
Screening.
11. History of interstitial lung disease.
12. Receipt of live attenuated vaccines within 30 days prior to the first dose of IP.
Patients, if enrolled, should not receive live or live attenuated vaccines during the
study and for 30 days after the last dose of IP.
13. The patient is the Investigator, sub-investigator or anyone directly involved in the
conduct of the study.
14. History or current evidence of any condition or disease that could confound the
results of the study or, in the opinion of Investigator, is not in the best interest
of the patient to participate.
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