Phase 2 Study of WGI-0301 for Advanced HCC

NCT06309485 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: WGI0301-P2G-01
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 4

Brief 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.

Conditions

Advanced Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (1)

• Efficacy of WGI-0301 in combination with Sorafenib based on ORR per RECIST 1.1.

  ORR is defined as the percentage of patients documented to have a confirmed CR or PR.

  through study completion, an average of 2 year

Secondary Outcomes (8)

• Safety of each dose group.

  through study completion, an average of 2 year

• Tolerability of each dose group.

  through study completion, an average of 2 year

• Anti-tumor activity if WGI-0301 in combination with Sorafenib based on ORR.

  through study completion, an average of 2 year

• Anti-tumor activity if WGI-0301 in combination with Sorafenib based on DCR.

  through study completion, an average of 2 year

• Anti-tumor activity if WGI-0301 in combination with Sorafenib based on DoR.

  through study completion, an average of 2 year

Study Arms (3)

Arm A

EXPERIMENTAL

WGI-0301 at MTD / RP2D dose with standard dose Sorafenib

Drug: WGI-0301 at MTD/RP2D dose IV infusion, QW; Drug: Sorafenib 400 mg PO, BID

Arm B

EXPERIMENTAL

WGI-0301 at MTD / RP2D -1 dose with standard dose Sorafenib

Drug: WGI-0301 at MTD/RP2D -1 dose IV infusion, QW; Drug: Sorafenib 400 mg PO, BID continuously

Arm C

ACTIVE COMPARATOR

Standard dose Sorafenib alone

Drug: Sorafenib 400 mg PO, BID continuously

Interventions

WGI-0301 at MTD/RP2D -1 dose IV infusion, QW DRUG

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 B

Sorafenib 400 mg PO, BID continuously DRUG

Sorafenib is an oral multi-kinase inhibitor used for the treatment of hepatocellular carcinoma.

Arm B; Arm C

Sorafenib 400 mg PO, BID DRUG

Sorafenib is an oral multi-kinase inhibitor used for the treatment of hepatocellular carcinoma.

Arm A

WGI-0301 at MTD/RP2D dose IV infusion, QW DRUG

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 A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age on the day of signing informed consent, male or female.
• Voluntarily agree to provide signed informed consent and are willing and able to comply with all aspects of the protocol.
• Histologically or cytologically confirmed diagnosis of HCC, or clinical diagnosis of HCC as per 2018 AASLD criteria.
• BCLC Stage C or BCLC Stage B with bilobar involvement and infiltrative nature that is only suitable for systemic anti-tumor therapy, and not suitable for any curative surgeries, liver transplantation, or local therapy (BCLC Classification see Appendix 6, Section 14.6).
• Stage 1 only: At least first-line standard treatment failure (disease progression confirmed by imaging) with no available standard treatment options, or unsuitability for standard treatment, or intolerance to standard treatment.
• Stage 2 only: At least first-line standard treatment failure (disease progression confirmed by imaging) or intolerance.
• Stage 3 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).
• Stage 2 and Stage 3: Eligible for treatment with Sorafenib as determined by investigators according to the Package Insert and clinical judgment.
• ECOG PS of 0 or 1 within 7 days prior to the first dose of study intervention.
• 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.
• Life expectancy in the judgement of the Investigator \> 12 weeks.
• 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 on supportive therapy, such as alopecia, Grade 2 peripheral neuropathy, and hypothyroidism stabilized on hormone replacement therapy.
• Stage 2 and Stage 3:Collection of an archived tissue sample will be requested (where available) or agree to undergo tumor tissue biopsy for biomarker testing; 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.
• Patients must have adequate organ function as defined below:
• Child-Pugh Liver Function Class A or Class B (score ≤ 7) (see Appendix 7 in Section 14.7)

You may not qualify if:

• Pregnant or breastfeeding patients or expecting to conceive or father children within the projected duration of the study.
• Stage 2 and Stage 3: Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma.
• 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).
• Major surgery within 4 weeks prior to the first dose of study intervention.
• Previous identified allergy or hypersensitivity to components of WGI-0301 similar drugs or liposomal drugs or related excipients.
• Stage 2 and Stage 3: Previous identified allergy or hypersensitivity to components of Sorafenib or similar drugs.
• Stage 3 only: Received prior Sorafenib therapy or any agents targeting AKT-PI3K pathway.
• 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 (except for observational clinical trials).
• Locoregional therapy to liver within 4 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).
• Small molecule targeted therapy and traditional Chinese medicine with antitumor indications received within 2 weeks prior to the first dose, or chemotherapy, biological therapy, and other antitumor treatments received within 4 weeks prior to the first dose.
• Stage 2 and Stage 3：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.
• Clinically significant abnormalities of glucose metabolism (e.g., Patients with diabetes mellitus type1 or diabetes mellitus type 2 requiring treatment, or those with HbA1c ≥8.0%.
• 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.

Sponsors & Collaborators

• Zhejiang Haichang Biotech Co., Ltd.: lead

Study Sites (4)

China Pharmaceutical University, Shanghai Gobroad Cancer Hospital

Shanghai, Shanghai Municipality, 200131, China

RECRUITING

West China Hospital Sichuan University

Chengdu, China

RECRUITING

Sir Run Run Shaw Hospital Zhejiang University School of Medicine

Hangzhou, China

RECRUITING

Prince of Wales Hospital

Hong Kong, Hong Kong

NOT YET RECRUITING

MeSH Terms

Interventions

Sorafenib; BID protein, human

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Angela Men, MD., Ph.D

CONTACT

+1 2407020080; angela.men@thewogroup.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2024
• First Posted: March 13, 2024
• Study Start: July 31, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3); HK (1)