Safety, Tolerability and Anti-tumour Activity Study of MTL-CEBPA Plus Sorafenib

• Status: Not yet recruiting
• Trial end date: 2025-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase II study in patients with advanced liver cancer (hepatocellular carcinoma) caused by a hepatitis B and/or C infection. Participants will be dosed with a combination of MTL-CEBPA (an experimental treatment) and sorafenib. The MTL-CEBPA is administered once a week via intravenous infusion for three consecutive weeks followed by a week of rest (one cycle). Sorafenib is taken orally from Day 8 at a dose of 400 mg twice a day. Participants will receive cycles of treatment until disease progression, unacceptable toxicity, withdrawal of consent or death occurs.This combination of treatment was tested in a previous Phase I study (OUTREACH) which showed anti-tumour activity along with a good safety and toxicity profile.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mina Alpha Limited
• Treatments: Sorafenib

Criteria

Inclusion Criteria:

• Histologically confirmed advanced HCC with cirrhosis arising in a patient with a history of - Hepatitis B and/or C

• Child-Pugh classification A

• Patients considered unsuitable for liver tumour resection and/or refractory to loco regional therapy

• Patients naïve to TKIs [including sorafenib, regorafenib, cabozantinib, and lenvatinib]

• Life expectancy greater than 3 months at time of recruitment

• At least one measurable liver lesion (RECIST 1.1) with target lesion size more than 1 cm as measured by CT scan orMRI

• Platelet count > 60 x10 9/L

• Serum albumin ≥ 28g/L

• ALT and AST ≤ 5 x ULN

• Bilirubin ≤ 50 μmol /L

• WBC ≥ 2.0 x 10 9/L

• Absolute neutrophil count ≥ 1.5 x 10 9/L• Haemoglobin ≥ 9.0 g/dL

• INR < 1.5

• Calculated creatinine clearance ≥ 50 mL/min (Cockcroft & Gault or equivalent according to local practice at Investigator site)

• Negative blood pregnancy test for women of childbearing potential (within 10 days prior to first drug administration)

• For women of child-bearing potential, agreement to use highly effective contraception (defined as method(s) that result in a failure rate of < 1% per year) in females of childbearing potential during the entire study and defined post-study period

• For male participants with partners of child-bearing potential agreement to use barrier contraception plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least three months after the last dose of MTL-CEBPA (see additional information / requirements in Section 5.1.)

• Able to comply with all the requirements of the protocol

Exclusion Criteria:

• Child-Pugh classification B and C

• Patients without a history hepatitis B and/or hepatitis C

• Patients who have received TKI prior to the study or any other systemic therapy (chemotherapy, CPI, other clinical study agents)

• Patients who received investigational drug(s) within the last 30 days prior to study treatment initiation

• Any episode of bleeding from oesophageal varices or other uncontrolled bleeding within the last 3 months prior to study treatment initiation

• Patients with history of haemorrhage or gastrointestinal perforation

• Known infection with human immunodeficiency virus (HIV)

• Patients that had other malignancies in the last five years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death

• Patients with central nervous system (CNS) metastasis

• Patients presenting with a marked baseline prolongation of QT/QTc interval defined as repeated demonstration of a QTc interval≥ 450ms (males) and ≥ 460ms (females) using Fridericia's correction formula.

• Signs and symptoms of heart failure characterised as greater than New York Heart Association (NYHA) Class I or other clinically significant cardiac abnormalities (such as myocardial infarction) including stable abnormalities

• Major surgery within the last 30 days prior to study treatment initiation

• Patients with history of organ transplantation or cardiac surgery

• Patients with sepsis, ineffective biliary drainage with or without cholangitis, obstructive jaundice or encephalopathy at screening visit or within the last two weeks prior to study treatment initiation, whichever is earlier

• Evidence of spontaneous bacterial peritonitis or renal failure, or allergic reaction at screening visit or within the last two weeks prior to study treatment initiation, whichever is earlier

• Pregnant or lactating women