| Eligibility |
Inclusion Criteria:
1. Males or females = 18 years of age
2. Histologically confirmed and documented locally advanced or metastatic HCC that is
deemed not appropriate for curative therapy and Histologically confirmed and
documented locally advanced or metastatic iCCA.
3. Liver tumor burden< 50% of the liver (per Investigator judgment)
4. Antiviral therapy required in hepatitis B virus patients (Hepatitis B antigen
positive)
5. Willing to have liver biopsy at the beginning of cycle 2 (Day 1)
6. Presence of a measurable tumor per RECIST v1.1 criteria
7. Eastern Cooperative Oncology Group (ECOG) performance status = 1
8. Life expectancy = 12 weeks
9. Adequate hematologic function prior to the first dose of GNS561, defined as:
1. Absolute neutrophils count = 1500 cells/µL
2. Hemoglobin = 10 g/dL with no transfusion within 4 weeks prior to first planned
dose of GNS561
3. Platelet count > 50,000/µL with no transfusion within 2 weeks prior to first
planned dose of GNS561
10. Adequate renal function prior to first dose, defined as
1. Serum creatinine < 1.5 ULN
2. Creatinine clearance = 50 mL/min/m2 (by Cockroft-Gault equation of 24-hour urine)
if creatinine = 1.5 X ULN
11. Adequate hepatic function prior to first dose, defined as AST/ALT = 5 X ULN
12. Women patients of childbearing potential must have a negative serum/urine pregnancy
test at screening and baseline, and be willing to use a medically acceptable form, as
judged by Investigator and Sponsor, of contraception (e.g., hormonal birth control,
intrauterine device [IUD], or barrier method [male condom, female condom, diaphragm]),
plus a spermicidal agent [contraceptive foam, jelly, or cream]) or abstinence or
bilateral occlusion or whose partner had a vasectomy at least 2 years before
screening. The patient should be advised to continue the contraception for at least 6
months following the completion of dosing. Women with cessation for > 24 months of
previously occurring menses, or women of any age who have had a hysterectomy, or have
had both ovaries removed will be considered to be of non-childbearing potential.
13. Male patients of reproductive potential must be willing to use one acceptable method
of contraception, as judged by Investigator and Sponsor, as described in Criteria 12
and/or to refrain from donating sperm from the time of screening through at least 6
months following the completion of dose administration.
14. Amenable to computed tomography (CT) with 3 or 4 phase liver or magnetic resonance
imaging (MRI) of abdomen and pelvis, and CT of chest, or MRI of whole body, for
initial tumor size measurements and subsequent follow-up.
15. Absence of other clinically relevant abnormalities for screening laboratory test
results as judged by the Investigator and Sponsor.
16. Willingness and ability to comply with scheduled visits, treatment plan, laboratory
tests, and other study procedures.
17. Be willing to abstain from alcohol from signing of informed consent through Week 5
(completion of PK sampling at the beginning of Cycle 2).
18. Able to understand and provide written informed consent.
Exclusion Criteria:
1. Pregnant or breast-feeding mothers
2. Any known history of encephalopathy
3. Known esophageal varices with recent history of bleeding (within previous 2 months)
4. Clinically significant ascites or paracentesis
5. Known untreated or symptomatic brain metastases
6. Presence of residual toxicities of = Grade 2 after prior antitumor therapy = 4 weeks
prior to first dose. Grade 1 toxicities related to previous treatments are acceptable
at the time of the first planned dose of GNS561, as well as any alopecia.
7. Chronic treatment with immunosuppressive agents (like steroids) = 6 weeks prior to
first planned dose of GNS561.
8. Major surgical procedures, open biopsy or significant traumatic injury = 4 weeks prior
to first dose of GNS561 or anticipation of major surgical procedure during the course
of the trial, minor surgical procedures = 1 week of first planned dose
9. Any clinically significant cardiovascular condition as judged by the Investigator
10. Severe or uncontrolled renal condition
11. Untreated chronic hepatitis B
12. Known history of immunodeficiency diseases (e.g., active HIV)
13. Use of any prohibited concomitant medications within 14 days of the Baseline/Day 1
visit
14. Known current alcohol (> 20g/ Day in women and > 30g/ Day in men) or substance abuse
15. Malabsorption issues (e.g., gastric bypass or gastrectomy patients)
16. Participation in any investigational clinical investigation = 4 weeks prior to first
planned dose of GNS561 or longer if required by local regulations, and for any other
limitation of participation based on local regulations
17. Known clinically significant or life threatening organ or systemic disease such that
in the opinion of the Investigator, the significance of the disease will compromise
the patient's participation in the trial
18. Is a participant or plans to participate in another investigational clinical study,
while taking part in this study.
19. Known intolerance or hypersensitivity to the active ingredient or to one of the
components of the study drug
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