Oncolytic Virotherapy Plus PD-1 Inhibitor and Lenvatinib as Second-line or Later Therapy in Patients With Advanced Hepatocellular Carcinoma

NCT05675462 | Unknown Phase 1

• 1 other identifier: OPTIONS-04
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to evaluate the safety/tolerability efficacy of oncolytic virotherapy combined with Tislelizumab plus lenvatinib as second-line or later therapy in patients with advanced hepatocellular carcinoma.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (5)

• Dose Limiting Toxicities (DLT)

  The DLT assessment period is defined as: Day of Injection through 28 days post injection (Safety Follow Up). A DLT will be defined as any Grade 3 or higher adverse event, as assessed by the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.

  28 days

• Maximum tolerated dose

  A MTD is determined if any cohort experiences 2 subjects with DLT's. Safety

  max 24 months

• Adverse event (AE).

  max 24 months

• Treatment emergent adverse event(TEAE).

  max 24 months

• Serious adverse event (SAE).

  max 24 months

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  max 24 months

• DoR

  max 24 months

• PFS

  max 24 months

• OS

  max 42 months

• DCR

  max 24 months

Study Arms (1)

H101 + Tislelizumab+ Lenvatinib

EXPERIMENTAL

(Dose escalation and cohort expansion) H101 administered by intratumoral injection in combination with Tislelizumab administered intravenously (IV), and Lenvatinib administered orally. H101 intratumorally injection starts at day 0. Tislelizumab plus lenvatinib will be initiated on day 1. Tislelizumab will be administered at 200 mg i.v. every 3 weeks plus a lenvatinib (bodyweight ≥ 60 kg, 12 mg; \< 60 kg, 8 mg) orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Drug: Oncorine; Drug: Tislelizumab; Drug: Lenvatinib

Interventions

Oncorine DRUG

a modified human recombinant type 5 adenovirus with genetic modifications

Also known as: H101

H101 + Tislelizumab+ Lenvatinib

Tislelizumab DRUG

PD-1inhibitor

H101 + Tislelizumab+ Lenvatinib

Lenvatinib DRUG

TKI

H101 + Tislelizumab+ Lenvatinib

Eligibility Criteria

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

You may qualify if:

• Written informed consent obtained.
• Age ≥ 18 years at time of study entry.
• Participants must have unresectable or metastatic histologically or cytologically confirmed hepatocellular carcinoma.
• Participants must have failed 1 line of systemic regimens for advanced hepatocellular carcinoma due to disease progression or toxicity.
• Patients had been refractory or intolerant to previous systemic chemotherapy (oxaliplatin-based chemotherapy), targeted therapy (eg, sorafenib or lenvatinib), or anti-PD-1 or anti-PD-L1 based regimen.
• At least one measurable site of disease as defined by RECIST criteria with spiral CT scan or MRI.
• Performance status (PS) ≤ 2 (ECOG scale).
• Life expectancy of at least 12 weeks.
• Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥ 1,500/L, platelets ≥75 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula )
• Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.

You may not qualify if:

• History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment
• Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
• RFA and resection administered less then 4 weeks prior to study treatment start.
• Radiotherapy administered less then 4 weeks prior to study treatment start.
• Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery.
• Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix.
• Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).
• Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study Treatment or interpretation of patient safety or study results, including but not limited to:
• history of interstitial lung disease
• Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection)
• known acute or chronic pancreatitis
• active tuberculosis
• any other active infection (viral, fungal or bacterial) requiring systemic therapy
• history of allogeneic tissue/solid organ transplant
• diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of Tislelizumab treatment.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

tislelizumab; lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Central Study Contacts

Peng Wang, MD

CONTACT

86-21-64175590; wangp413@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 29, 2022
• First Posted: January 9, 2023
• Study Start: March 1, 2023
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: March 6, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)