Advanced hepatocellular cancer (HCC) as result of hepatitis B and/or hepatitis C MedDRA version: 20.0 Level: PT Classification code 10073071 Term: Hepatocellular carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10036706 Term: Primary liver cancer non-resectable System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.1 Lev
Conditions
Interventions
Product Name: MTL-CEBPA
Product Code: MTL-CEBPA
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: CEBPA-51
Other descriptive nam
Sponsors
MiNA Alpha Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent obtained prior to any specific trial-related procedure 2. Male or female 18 years or older. 3. Histologically confirmed advanced HCC with cirrhosis in a participant with a history of hepatitis B and/or C. Participants with past or ongoing HCV infection will beeligible for the study. Participants must have completed their treatment at least 1 month prior to starting study intervention and their HCV viral load below the limit ofquantification. Participants who are HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution will be eligible. Participants with past or controlled ongoing hepatitis B will be eligible as long as their HBV viral load is less than 500 IU/mL prior to first dose of study drug. Participants on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study intervention. 4. Child-Pugh classification A. 5. Unsuitable for liver tumour resection and/or refractory to loco regional therapy. 6. Not eligible for liver transplantation. 7. Had progression or recurrence of HCC following previous treatment with atezolizumab in combination with bevacizumab. Participants with progression or recurrence of HCC on non atezolizumab anti-PD-1/PD-L1 inhibitors and non-bevacizumab anti-VEGF agent in combination or as any as single agents, and no priortreatment with atezolizumab and bevacizumab, are eligible. 8. Naïve to tyrosine kinase inhibitors, including sorafenib, regorafenib, cabozantinib, and lenvatinib. 9. Participants with BCLC stage C disease. 10. Eastern Cooperative Oncology Group performance status of 0 or 1. 11. Has the ability to swallow and retain oral medication. 12. Life expectancy greater than 3 months at time of recruitment. 13. At least one measurable liver lesion (RECIST v1.1) assessed by the investigator. 14. Platelet count >70 x 109/L. 15. Serum albumin =28 g/L. 16. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =5 x the upper limit of normal (ULN). 17. Bilirubin =50 µmol /L. 18. White Blood Cell (WBC) =2.0 x 109/L. 19. Absolute neutrophil count =1.5 x 109/L. 20. Haemoglobin =9.0 g/dL. 21. International Normalized Ratio (INR) <1.5. 22. Calculated creatinine clearance =50 mL/min (Cockcroft & Gault). 23. AEs due to prior therapy must have resolved to Grade =1 24. Negative blood pregnancy test for women of childbearing potential (within 10 days prior to first drug administration). Note: a woman is considered of child-bearing potential following menarche and until becoming post-menopausal unless permanently sterile. Permanent methods ofsterilisation include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A post-menopausal state is defined as no menses for 12 months without analternative medical cause. Female participants of childbearing potential must use highly effective* contraceptive measures adequate to prevent a new pregnancy for the duration of the studytreatment with MTL-CEBPA and sorafenib and, in addition, for at least six months after the last dose of MTL-CEBPA and six months beyond the last dose of sorafenib, as recommended in sorafenib’s U.S. Package Insert (USPI). For women with reproductive potential who use a hormonal method of contraception, concurrent use of a second (barrier) method is recommended. 25. Male participants with partners of child-bearing potential must use highly effective contraception and are required to use barrier contraception plus an additionalcontraceptiv
Exclusion criteria
Exclusion criteria: 1. Child-Pugh classification B and C. 2. Participants without a history of hepatitis B and/or hepatitis C. 3. Participants with fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtype HCC. 4. Participants with no prior therapy who are eligible for first-line treatment with atezolizumab in combination with bevacizumab. 5. Participants who received investigational drug(s) within the last 30 days prior to study treatment initiation. 6. Participants with clinically significant ascites. 7. Any episode of bleeding from oesophageal varices or other uncontrolled bleeding including clinically meaningful epistaxis within the last 3 months prior to study treatment initiation. 8. Clinically diagnosed hepatic encephalopathy in the last 6 months unresponsive to therapy. 9. Participants with a history of gastrointestinal haemorrhage or perforation. 10. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated such metastases may participate provided they are radiologically stable for at least 4 weeks by repeat imaging performed during study screening, clinically stable and without requirement of steroid treatment for at least 28 days prior to first dose of study intervention. MRI brain scan are required for all participants with stable brain metastases at screening (CT scan will be allowed if MRI is contraindicated). 11. Participants administered with serum albumin within the last 7 days prior to the first study treatment administration. 12. Known infection with human immunodeficiency virus (HIV) with CD4+ T-cell counts 90 mm Hg. 17. Clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted. 18. Major surgery within the last 30 days prior to study treatment initiation. If the participant had major surgery, the participant must have recovered adequately fromthe procedure and/or any complications from the surgery prior to starting study interve
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare Progression Free Survival (PFS) (ie the time between randomisation until the 1st documented progression in the size of their tumour) of MTL-CEBPA in combination with sorafenib compared to sorafenib alone as determined by Blinded Independent Central Review (BICR) and assessed using RECIST v1.1 guidelines(standard guidelines for assessing the progression of tumours);Secondary Objective: To compare efficacy of MTL-CEBPA in combination with sorafenib compared to sorafenib alone as assessed by a blinded independent central assessor for the following: Best Objective Response (BOR), Objective Response Rate (ORR), Duration of Response (DoR), Time to Response (TTR), and changes in tumour size.To compare Overall Survival of MTL-CEBPA in combination with sorafenib compared to sorafenib alone. To assess consistency in tumour-based efficacy endpoints between independent assessment and Investigator assessment. To evaluate the safety and tolerability profile of MTL-CEBPA when administered in combination with sorafenib and compared to sorafenib alone. To compare the health-related quality of life (HRQoL) of MTL-CEBPA in combination with sorafenib compared to sorafenib alone as assessed by EORTC-QLQ-C30plus EORTC-QLQ-HCC18 QOL questionnaires.;Primary end point(s): Progression Free Survival (PFS) by RECIST V1.1 assessed by Blinded Independent Central Reviewer;Timepoint(s) of evaluation of this end point: PFS is defined as the time from randomisation until the date of first documented progression (per RECIST v1.1) or death due to any cause in the absence of progression, whichever occurs first. It will be analysed by Intention to Treat (ITT), which will include all randomised participants. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Best Objective Response (BOR), Overall Response Rate (ORR), Duration of Response (DoR), Time to Response (TTR) and changes in tumour size by RECIST v1.1 assessed by BICR. 2. Overall Survival. 3. Progression Free Survival (PFS), BOR, ORR, DOR, TTR and changes in tumour size by RECIST v1.1 assessed by Investigator and BICR. 4. Incidence of AEs/serious AEs (SAE) and laboratory test results graded according to toxicity criteria (CTCAE v5.0 November 27, 2017), vital signs and ECG. 5. Change over time in scores from EORTC-QLQ-C30 and EORTC-QLQ-HCC18 QoL questionnaires.;Timepoint(s) of evaluation of this end point: BOR is best response recorded from start of treatment until disease progression, last evaluable assessment in absence of progression, or start of new subsequent anti-cancer therapy. ORR is calculated as number and % of participants with BOR response of Complete Response or Partial Response in the size of tumour DoR is defined as time from date of first documented tumour response (CR/PR) until progression/death. TTR is defined as the time from randomization to the date of the first documented tumour response (CR/PR). Time to response will be summarised descriptively bytreatment arm. Tumour size is defined as the sum of the diameters (SoDs) of the RECIST v1.1 target lesions. OS is defined as the time between the date of randomisation and the date of death from any cause | — |
Countries
Australia, Austria, Belgium, France, Germany, Hong Kong, Korea, Republic of, Netherlands, Singapore, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactAlison Adderkin
MiNA Alpha Limited
Outcome results
None listed