Trial Title:
Phase 2 Study of WGI-0301 for Advanced HCC
NCT ID:
NCT06309485
Condition:
Advanced Hepatocellular Carcinoma (HCC)
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Sorafenib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
WGI-0301 at MTD/RP2D dose IV infusion, QW
Description:
WGI-0301 is a lipid nanoparticle preparation of Archexin®, a 20-mer oligonucleotide that
is complementary to Akt-1 mRNA, formulated for the treatment of advanced HCC.
Arm group label:
Arm A
Intervention type:
Drug
Intervention name:
WGI-0301 at MTD/RP2D -1 dose IV infusion, QW
Description:
WGI-0301 is a lipid nanoparticle preparation of Archexin®, a 20-mer oligonucleotide that
is complementary to Akt-1 mRNA, formulated for the treatment of advanced HCC.
Arm group label:
Arm B
Intervention type:
Drug
Intervention name:
Sorafenib 400 mg PO, BID continuously
Description:
Sorafenib is an oral multi-kinase inhibitor used for the treatment of hepatocellular
carcinoma.
Arm group label:
Arm B
Arm group label:
Arm C
Intervention type:
Drug
Intervention name:
Sorafenib 400 mg PO, BID
Description:
Sorafenib is an oral multi-kinase inhibitor used for the treatment of hepatocellular
carcinoma.
Arm group label:
Arm A
Summary:
The purpose of this study is to determine the MTD of WGI-0301 in combination with
Sorafenib for advanced Hepatocellular Carcinoma (HCC) and assess its safety and efficacy
in adults with advanced unresectable HCC who have previously received PD-1 / PD-L1 immune
checkpoint inhibitors.
Detailed description:
This study will include a two-stage design: Stage 1 (dose escalation) to determine the
MTD/RP2D of WGI-0301 combined with Sorafenib. Stage 2 (dose expansion) with two different
dose levels of WGI-0301 in combination with standard dose Sorafenib, or standard dose
Sorafenib alone.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. ≥18 years of age on the day of signing informed consent, male or female.
2. Voluntarily agree to provide signed informed consent and are willing and able to
comply with all aspects of the protocol.
3. Histologically or cytologically confirmed diagnosis of HCC. Diagnosis of HCC can be
made without a biopsy if radiographic hallmarks of arterial hypervascularity and
venous/ late phase washout are present by either dynamic contrast enhanced MRI or
helical multidetector CT scan using contrast for a lesion > 2 cm, or by both
modalities for a lesion 1~2 cm.
4. Barcelona Clinic Liver Cancer (BCLC) Stage C or BCLC stage B with bilobar
involvement and infiltrative nature that is not amendable for local therapy (BCLC
Classification see Appendix 7, Section 14.7).
5. Stage 1 only: At least first-line standard treatment failure (disease progression
confirmed by imaging) or intolerance with no restriction on the number of prior
lines of systemic treatment.
6. Stage 2 only: Patients must have objective radiographic disease progression or
intolerance (Intolerance is defined as currently discontinued after ≥28 days of
treatment due to toxicity) after only one prior line of systemic immunotherapy
treatment with an anti-PD-1/ PD-L1 mAb administered either as monotherapy or in
combination with other checkpoint inhibitors or other therapies (Prior locoregional
therapy such as surgery, radiofrequency ablation or trans-arterial chemoembolization
are also allowed but not counted as systemic therapy, provided that progression has
been documented after these therapies, and ≥4 weeks have elapsed since the last
therapy).
7. Eligible for treatment with Sorafenib, as determined by investigators according to
the Package Insert and clinical judgment.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 within 7
days prior to the first dose of study intervention.
9. Patients must have at least one measurable lesion according to RECIST 1.1 as
determined by the investigator, and that has not been the target of local or
regional therapy including trans-arterial chemoembolization, intra-arterial
chemotherapy, ethanol, or radiofrequency ablation; a new area of tumor progression
within or adjacent to a previously treated lesion, if clearly measurable by a
radiologist, is acceptable.
10. Stage 2 only: Patients must have at least one target lesion according to mRECIST
that meet all the following criteria:
- The lesion can be classified as a RECIST 1.1 measurable lesion.
- The lesion is suitable for repeat measurement.
- The lesion shows intratumoral arterial enhancement on contrast-enhanced CT or
MRI.
11. Life expectancy in the judgement of the Investigator > 12 weeks.
12. Recovery to ≤ Grade 1 (CTCAE V5.0) from toxicities related to any prior treatments
unless the adverse events are clinically non-significant and/ or stable with or
without supportive therapy, except for alopecia (any grade) and Grade 2 peripheral
neuropathy.
13. Collection of an archived tissue sample will be requested (where available) to
support evaluation of the clinical utility of biomarker assessment in newly obtained
vs. archived tissue samples; however, a subject will not be precluded from
participating in the study if tissue sample is not available for collection or is
otherwise insufficient for analysis.
14. Patients must have adequate organ function as defined below (Specimens must be
collected within 7 days prior to the start of study intervention):
- Child-Pugh Liver Function Class A (see Appendix 6 in Section 14.6)
- AST or ALT ≤ 5.0 × ULN and total bilirubin ≤ 2 × ULN
- Serum albumin ≥ 2.8 g/ dL
- Creatinine Clearance (CrCL) ≥ 40 ml/ min (Cockcroft-Gault formula: CrCL (mL/
min) = [140-age(year)] × body weight (Kg)/ [72 × Scr (mg/ dl)]{ × 0.85 for
female subjects})
- International normalized ratio (INR) ≤ 2.0 (except for warfarin therapy)
- Hemoglobin ≥ 8.5 g/ dL, absolute neutrophil count > 1000/ mm3, platelet
count ≥ 60 000/ mm3 (no blood transfusion or blood products or granulocyte
colony-stimulating factor within 14 days, corrected with erythropoietin or
darbepoetin α are allowed)
15. Participants with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection will
be allowed if they meet the following criteria:
- HBV-HCC: Resolved HBV infection (as evidenced by detectable HBV surface
antibody, detectable HBV core antibody, undetectable HBV DNA, and undetectable
HBV surface antigen) or chronic HBV infection (as evidenced by detectable HBV
surface antigen or HBV DNA). Subjects with chronic HBV infection must have HBV
DNA < 500 IU/ mL and must be on antiviral therapy. Active or uncontrolled
clinically serious HBV infections are excluded.
- HCV-HCC: Stable or resolved HCV infection (as evidenced by detectable HCV RNA
or antibody).
16. No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer
from which the patient is currently in complete remission per investigators'
clinical judgment.
17. Women of child-bearing potential must have a negative urine or serum pregnancy
within 3 days prior to receiving the first dose of study medication and must use
accepted highly effective methods of contraception from the time of signing the
informed consent through 6 months after the last dose of study drug. Men treated or
enrolled on this protocol must also agree to use adequate contraception prior to the
study, or be surgically sterile, for the duration of study participation, and for 3
months after completion of study drug administration. See Appendix 1 for
protocol-approved highly effective methods of contraceptive combinations.
Exclusion Criteria:
1. Pregnant or breastfeeding patients or expecting to conceive or father children
within the projected duration of the study.
2. Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma.
3. Complete occlusion of the major portal vein or vena cava due to HCC (The major
portal vein is defined as the part of portal vein between the union of the splenic
and superior mesenteric veins and the first bifurcation into the left and right
vein).
4. Major surgery within 4 weeks prior to the first dose of study intervention.
5. Previous identified allergy or hypersensitivity to components of WGI-0301 similar
drugs or liposomal drugs or related excipients.
6. Previous identified allergy or hypersensitivity to components of Sorafenib or
similar drugs.
7. Stage 2 only: Received prior Sorafenib therapy or any agents targeting AKT-PI3K
pathway.
8. Currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks prior to the first dose of study intervention.
9. Locoregional therapy to liver within 6 weeks prior to the first dose, including but
not limited to TACE, radiotherapy, radiofrequency ablation, microwave (except
palliative radiotherapy for bone pain relief completed at least 2 weeks prior to the
first dose).
10. Patients on concomitant use of strong CYP3A4 inducers (see Appendix 3 in Section
14.3) within 12 days prior to the first dose of study intervention. Additionally,
patient in use of transporters based on FDA Drug Development and Drug Interactions,
Table of Substrates, Inhibitors, and Inducers, or strong inducers of transporter,
P-gp, including apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin,
rifampin, St. John's wort. Patient in use of strong inhibitors of transporters based
on based on FDA Drug Development and Drug Interactions, Table of Substrates,
Inhibitors, and Inducers.
11. Clinically significant abnormalities of glucose metabolism (e.g., Patients with
diabetes mellitus type1 or diabetes mellitus type 2 requiring treatment, or those
with hemoglobin A1c (HbA1c) ≥8.0%.
12. clinically significant cardiovascular disease including:
- Uncontrolled chronic hypertension defined as systolic > 150 mmHg or diastolic >
90 mmHg on more than one measurement despite optimal therapy (initiation or
adjustment of BP medication prior to study entry is allowed provided that the
average of 3 BP readings prior to enrollment is < 150/ 90 mmHg).
- Hypotension as indicated by systolic blood pressure < 90 mmHg or mean arterial
pressure < 65 mmHg on 2 consecutive measurements at the Screening Visit.
- NYHA class III or IV Congestive heart failure, myocardial infarction or stroke,
unstable angina pectoris, pericardial effusion (excluding trace pericardial
effusion identified by echocardiography) or left ventricular ejection fraction
< 45% within 6 months prior to the first dose.
- Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic
cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive
cardiomyopathy, indeterminate cardiomyopathy).
- Bradycardia (known history of cardiovascular disease and either physical
examination at rest or electrocardiogram indicating heart rate < 50 bpm), or
screening ECG indicating QTcF ≥ 470 msec, 2 retests at 30-minute intervals were
required for the first abnormal QTcF, and 3 mean values were taken, Or there is
severe arrhythmia requiring further treatment, including but not limited to
ventricular fibrillation, atrial fibrillation, sustained ventricular
tachycardia, second-degree or third-degree atrioventricular block, torsades de
pointes, etc.
13. Clinically significant gastrointestinal disorders including:
- Medical history of difficulty swallowing, malabsorption, or other chronic
gastrointestinal disease, or conditions that may hamper compliance and/ or
absorption of the tested products
- Gastrointestinal perforation and/ or fistula intra-abdominal abscess or
intestinal obstruction within 6 months prior to the first dose
- Clinically significant gastric bleeding within 6 months prior to the first dose
(patients may be enrolled if esophageal and gastric varices are present on
imaging, but no bleeding event or inpatient medical intervention occurs within
6 months prior to the first dose)
14. Clinically significant bleeding risks including:
- Known hereditary or acquired bleeding or thrombotic tendencies (e.g.,
hereditary hemorrhagic telangiectasia or von Willebrand disease)
- Bleeding symptoms such as hemoptysis (> 1/ 2 teaspoon bright red blood) and
gastrointestinal bleeding within 3 months prior to screening
- Thrombolytic agents within 10 days prior to the first dose
- Receiving anticoagulant therapy (e.g., anticoagulants, antiplatelets) with an
unstable anticoagulant regimen and/ or dosage (except sodium heparin for
maintenance of central venous catheter patency)
15. History of solid organ transplant.
16. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS) related illness or is receiving systemic steroid therapy or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study
intervention.
17. Known active or uncontrolled infection that could interfere with the study.
18. Uncontrolled ascites or pleural effusion requiring repeated drainage (investigator's
judgment).
19. Past or current history of neoplasm other than HCC, except for curatively treated
nonmelanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively
treated and with no evidence of disease for at least 3 years.
20. Known central nervous system (CNS) or brain metastasis that is either symptomatic or
untreated.
21. History of drug abuse or addiction at the present stage.
22. Subject has any other conditions or reason that, in the opinion of the Investigator,
interferes with the ability of the subject to participate in the trial, places the
subject at undue risk or complicates the interpretation of data.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
August 2024
Completion date:
December 2026
Lead sponsor:
Agency:
Zhejiang Haichang Biotech Co., Ltd.
Agency class:
Industry
Source:
Zhejiang Haichang Biotech Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06309485
