A Study to Evaluate MIV-818 in Patients With Liver Cancer Manifestations

NCT03781934 | Completed Phase 1 DMC

• 1 other identifier: MIV-818-101/201
• Study Type: interventional
• Target: 53
• Locations: 4 countries
• Sites: 18

Brief Summary

This is an open-label, multicentre dose escalation/expansion study to assess safety and tolerability of MIV 818 as either monotherapy or in combination with 1) lenvatinib, a tyrosine kinase inhibitor used as a standard of care for the treatment of HCC or 2) pembrolizumab, a PD-1 inhibitor. The monotherapy parts of the study will include patients with various solid tumours that have spread to the liver, or alternatively originating in the liver. Evaluations of MIV-818 in combination with lenvatinib or pembrolizumab will only include patients with HCC.

Conditions

Hepatocellular Carcinoma; Intrahepatic Cholangiocarcinoma; Liver Metastases

Outcome Measures

Primary Outcomes (9)

• Incidence and Severity of Adverse Events (AEs)

  Percentage of participants with an adverse event, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0

  Participants monitored throughout treatment period and during follow-up, up to 6 months

• Incidence and magnitude of clinically significant changes in red blood cell count, white blood cell count and platelet count

  Change from baseline

  Participants monitored throughout treatment period and during follow-up, up to 6 months

• Incidence and magnitude of clinically significant changes in aspartate aminotransferase (AST) and alanine aminotransferase (ALT)

  Change from baseline

  Participants monitored throughout treatment period and during follow-up, up to 6 months

• Incidence and magnitude of clinically significant changes in bilirubin

  Change from baseline

  Participants monitored throughout treatment period and during follow-up, up to 6 months

• Incidence of clinically significant changes in vital sign - Systolic and diastolic blood pressure

  Millimeter of mercury (mmHg)

  Participants monitored throughout treatment period and during follow-up, up to 6 months

• Incidence of clinically significant changes in vital sign - Pulse rate

  Beats per minute (BPM)

  Participants monitored throughout treatment period and during follow-up, up to 6 months

• Incidence of clinically significant changes in vital sign - Body Temperature

  Celsius (°C)

  Participants monitored throughout treatment period and during follow-up, up to 6 months

• Incidence of clinically significant changes in vital signs - Weight

  Kilograms (kg)

  Participants monitored throughout treatment period and during follow-up, up to 6 months

• Incidence of clinically significant changes in ECGs

  QT interval (milli second (ms))

  Participants monitored throughout treatment period and during follow-up, up to 6 months

Secondary Outcomes (2)

• Preliminary efficacy by means of RECIST evaluation

  Participants monitored throughout treatment period every 6 weeks until disease progression, up to 6 months

• Plasma levels of α fetoprotein (AFP)

  Participants monitored throughout treatment period every 6 weeks until disease progression, up to 6 months

Study Arms (2)

MIV-818 (fostroxacitabine bralpamide) + pembrolizumab

EXPERIMENTAL

Phase 2a expansion cohort HCC

Drug: MIV-818 (fostroxacitabine bralpamide) + pembrolizumab

MIV-818 (fostroxacitabine bralpamide) + lenvatinib

EXPERIMENTAL

Phase 2a expansion cohort HCC

Drug: MIV-818 (fostroxacitabine bralpamide) + lenvatinib

Interventions

MIV-818 (fostroxacitabine bralpamide) + pembrolizumab DRUG

MIV-818 - oral capsules; pembrolizumab - IV

MIV-818 (fostroxacitabine bralpamide) + pembrolizumab

MIV-818 (fostroxacitabine bralpamide) + lenvatinib DRUG

MIV-818 - oral capsules; lenvatinib - oral capsules

MIV-818 (fostroxacitabine bralpamide) + lenvatinib

Eligibility Criteria

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

You may qualify if:

• Male or female ≥ 18 years of age on the day of signing informed consent.
• Able to understand and voluntarily sign a written informed consent and is willing, and able, to comply with the protocol requirements.
• Must have measurable disease based on RECIST v1.1 as determined by the site study team. Must have at least 1 target lesion in the liver. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Must have a Child-Pugh A status for Phase 1a and a Child-Pugh A or B status for Phase 1b and 2a. SRC discretion to restrict to Child-Pugh A status for Phase 1b and 2a.
• Must have an ECOG performance status of 0 or 1 at Screening.
• Must have life expectancy of \> 12 weeks in the investigator's opinion.
• Must have ALT and AST ≤ 5.0 × upper limit of normal (ULN) at Screening.
• Must have total bilirubin (TBil) ≤ 3.0 mg/dL at Screening.
• Must have adequate renal function with estimated creatinine clearance
• ≥ 60 mL/min (based on Cockcroft and Gault formula or similar) at Screening
• Must have platelets ≥ 75,000/mL at Screening.
• Must have International Normalized Ratio (INR) ≤ 1.7 at Screening. Female who is postmenopausal, OR Female who is of childbearing potential (postmenarchal) who agrees to use a highly efficient method of contraception (ie, a method with less than 1% failure rate \[eg, sterilization, hormone implants, hormone injections, intrauterine devices, or vasectomized partner or combined birth control pills\]) from Screening until 90 days after the final dose of MIV-818.
• OR Male who agrees to use condoms from Screening until 90 days after the final dose of MIV-818.
• OR Male with a female partner of childbearing potential (WOCBP) who is using a highly efficient method of contraception as described above.
• \. WOCBP must have a negative serum pregnancy test at Screening and negative (serum or urine) pregnancy test within 72 h before the first study drug dose.

You may not qualify if:

• Tumor volume exceeding 50% of liver.
• History of previous malignancy within the last 5 years except basal cell carcinoma or carcinoma in situ in solid organ.
• Known CNS or brain metastases, unless previously treated and stable for 3 months.
• Ongoing significant disease other than target disease as judged by the investigator to compromise the patients' ability to complete this study.
• History of solid organ transplant or bone marrow transplant.
• Receiving immunosuppressive therapy including oral corticosteroids.
• Active hepatitis B (eg, hepatitis B surface antigen \[HBsAg\] reactive) and patients with active hepatitis C (eg, hepatitis C RNA is \[qualitative\] detected).
• Positive human immunodeficiency virus (HIV) infection.
• Poorly controlled ascites and/or requirement for therapeutic paracentesis more frequently than once every 3 months.
• Symptomatic encephalopathy within 3 months prior to Screening and/or requirement for medication for encephalopathy.
• Esophageal variceal bleeding within 2 weeks prior to Screening.
• Receiving prior anticancer therapy within 4 weeks prior to first dose of MIV-818.
• Receiving any other investigational agent within 4 weeks prior to Screening
• Enrolled in another clinical study with an investigational drug.
• Presence of residual toxicities of CTCAE Grade \> 1 after prior anticancer therapy within 2 weeks of first treatment with MIV-818, except for alopecia.

Sponsors & Collaborators

• Medivir: lead

Study Sites (18)

Antwerp University Hospital

Antwerp, 2650, Belgium

Location

University Hospitals Gasthuisberg

Leuven, 3000, Belgium

Location

CHA Bundang Medical Center

Gyeonggi-do, South Korea

Location

Pusan National University Hospital

Pusan, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital

Seoul, South Korea

Location

Hospital Clinic Carrer Rosselló 161

Barcelona, Spain

Location

Hospital Vall Hebrón

Barcelona, Spain

Location

START Barcelona HM Nou Delfos

Barcelona, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28009, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

START Madrid-FJD

Madrid, Spain

Location

Beatson West of Scotland Cancer Care

Glasgow, United Kingdom

Location

Guy's Hospital, Oncology and Clinical Trials

London, United Kingdom

Location

Northern Institute for Cancer Research

Newcastle upon Tyne, United Kingdom

Location

Chruchill Hospital, Cancer and Haematology Centre

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Cholangiocarcinoma

Interventions

pembrolizumab; 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

Study Officials

• Ruth Plummer, Professor

  Northern Institute for Cancer Research, Newcastle

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Intrapatient dose escalations continuing into interpatient dose escalations to end with dose expansion cohorts.

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: December 20, 2018
• Study Start: September 5, 2018
• Primary Completion: January 7, 2025
• Study Completion: June 16, 2025
• Last Updated: July 1, 2025

Record last verified: 2025-06

Locations

GB (4); BE (2); KR (6); ES (6)