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Hepatocellular CarcinomaPhase 1/2NCT03781934

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

A Phase 1/2 study testing MIV-818 (fostroxacitabine bralpamide) + pembrolizumab and MIV-818 (fostroxacitabine bralpamide) + lenvatinib in people with Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma, run by Medivir at 18 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
MIV-818 (fostroxacitabine bralpamide) + pembrolizumab and MIV-818 (fostroxacitabine bralpamide) + lenvatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
18 sitesin 4 countries
Study dates
5 Sep 2018to 16 Jun 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • 13. 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.
  • Phase 1a and 1b specific Inclusion Criteria:
  • 14. Must have progressed on or are intolerant of standard therapy with:
  • Histologically or cytologically confirmed HCC, including fibrolamellar HCC; patients with HCC that received their diagnosis according to the agreed international radiological guideline are also admissible upon agreement between the investigator and the medical monitor, or
  • Histologically or cytologically confirmed iCCA, or
  • Liver metastases from colon, rectal, or gastric solid tumors with limited extrahepatic tumor burden (any extrahepatic metastases should be limited to 1 other site and a maximum of 1 target lesion outside the liver).
  • Phase 1b Monotherapy-specific Inclusion Criterion:
  • 15. Must have:
  • Histologically or cytologically confirmed HCC, including fibrolamellar HCC; patients with HCC that received their diagnosis according to the agreed international radiological guideline are also admissible upon agreement between the investigator and the medical monitor, or
  • Histologically or cytologically confirmed iCCA, or
  • Liver metastases from solid tumors, with limited extrahepatic tumor burden (i.e. no brain or bone metastases), any extrahepatic metastases should be limited to 1 other site and a maximum of 1 target lesion outside the liver).
  • Combination therapy-specific Inclusion Criterion:
  • 16. Must have histologically or cytologically confirmed HCC that is considered advanced or unresectable, i.e. not suitable for either surgery, radiofrequency ablation (RFA) or loco-regional therapies (patients with HCC that received their diagnosis according to the agreed international radiological guideline are also admissible upon agreement between the investigator and medical monitor). Patients with fibrolamellar HCC or a mixed HCC and iCCA will be excluded.
  • 17. Must have progressed on or are intolerant of 1or 2 lines of standard therapy for HCC (see also exclusion criterion no. 20) and are now candidates for lenvatinib or pembrolizumab treatment.

Who cannot join

  • 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.
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  • 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.
  • History of allergic reactions attributed to compounds of similar chemical or biological composition to MIV-818.
  • HCC of diffuse infiltrative type.
  • Receiving drugs that are extensively metabolized by cytochrome P450 (CYP) 3A4 that have a narrow therapeutic index. Drugs that are extensively metabolized by CYP3A4 that have a narrow therapeutic index must be discontinued 5 half-lives before first dose of MIV-818.
  • Combination therapy-specific Exclusion Criteria:
  • Patients are excluded from combination therapy parts of this study if any of the following criteria are met:
  • Patients with a diagnosis of fibrolamellar HCC.
  • Received >2 lines of therapy for the treatment of advanced HCC.
  • Systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥100 mmHg despite optimal anti-hypertensive therapy and with no change in anti hypertensive agents within the last 1 week prior to Screening.
  • Women who are breastfeeding.
  • Bleeding disorders or receiving anti-coagulation drugs.
  • Any interventional treatment for esophageal varices required within 28 days of study treatment.
  • Hepatic encephalopathy in the last 6 months.
  • QTc interval is greater than 480 milliseconds at Screening.
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has an active infection requiring systemic therapy.
  • Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to planned start of study therapy.
  • Presence of known active tuberculosis (TB; Bacillus tuberculosis).
  • Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  • Known history of, or any evidence of active, non-infectious pneumonitis or has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Proteinuria > 1g / 24 hours. Patients with > 1+ proteinuria on dipstick testing will need a 24-hour urine protein measured to exclude proteinuria > 1g / 24 hours.

Trial locations and contacts

18 sites in 4 countries.

18 sites in 4 countries

South Korea6 sites
  • CHA Bundang Medical Center

    Gyeonggi-do

  • Pusan National University Hospital

    Pusan

  • Asan Medical Center

    Seoul

  • Samsung Medical Center

    Seoul

  • Seoul National University Hospital

    Seoul

  • Severance Hospital

    Seoul

Other trials in South Korea

Spain6 sites
  • Hospital Clinic Carrer Rosselló 161

    Barcelona

  • Hospital Vall Hebrón

    Barcelona

  • START Barcelona HM Nou Delfos

    Barcelona

  • Hospital General Universitario Gregorio Marañón

    Madrid, 28009

  • Hospital Universitario 12 de Octubre

    Madrid

  • START Madrid-FJD

    Madrid

Other trials in Spain

United Kingdom4 sites
  • Beatson West of Scotland Cancer Care

    Glasgow

  • Guy's Hospital, Oncology and Clinical Trials

    London

  • Northern Institute for Cancer Research

    Newcastle upon Tyne

  • Chruchill Hospital, Cancer and Haematology Centre

    Oxford, OX3 7LE

Other trials in United Kingdom

Belgium2 sites
  • Antwerp University Hospital

    Antwerp, 2650

  • University Hospitals Gasthuisberg

    Leuven, 3000

Other trials in Belgium

About this study

Official title: A Phase 1/2a Study in 3 Parts to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of MIV-818 in Patients With Liver Cancer Manifestations

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.

Read the detailed description

This study will be conducted in three phases. The initial phase, 1a, will enroll up to 12 subjects and include a total of one dose escalation per patient. Once pre-defined criteria for starting phase 1b monotherapy has been met among the enrolled patients in phase 1a, the next phase of the study will be initiated. Phase 1b monotherapy will enroll up to 30 patients in a 3+3 design with interpatient dose escalations. All dose escalation decisions will be made by a safety review committee that will meet regularly during the study conduct. When the MTD has been established, the SRC will provide a RP2D for monotherapy. Phase 1b combination constitutes an interpatient dose escalation to identify the RP2D for MIV-818 when used in combination with 1) lenvatinib and 2) pembrolizumab therapy. This part of the study will enroll up to 36 patients in a 3+3 design with interpatient dose escalations. Safety review will be performed by the SRC to determine the RP2D of MIV 818 for use in combination with lenvatinib and pembrolizumab. The SRC may recommend that the selected dose of MIV-818 is further evaluated in up to 30 patients in the Phase 2a expansion part of the study.

Being tested
MIV-818 (fostroxacitabine bralpamide) + pembrolizumab, MIV-818 (fostroxacitabine bralpamide) + lenvatinib
Medical subject headings
Carcinoma, Hepatocellular, Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MIV-818 (fostroxacitabine bralpamide) + pembrolizumabDrug

    MIV-818 - oral capsules; pembrolizumab - IV

  • MIV-818 (fostroxacitabine bralpamide) + lenvatinibDrug

    MIV-818 - oral capsules; lenvatinib - oral capsules

Study groups in NCT03781934
Study groupRoleWhat they receive
MIV-818 (fostroxacitabine bralpamide) + pembrolizumabExperimentalPhase 2a expansion cohort HCC
Receives: Drug: MIV-818 (fostroxacitabine bralpamide) + pembrolizumab
MIV-818 (fostroxacitabine bralpamide) + lenvatinibExperimentalPhase 2a expansion cohort HCC
Receives: Drug: MIV-818 (fostroxacitabine bralpamide) + lenvatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

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

    Change from baseline

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

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

    Change from baseline

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

  4. Incidence and magnitude of clinically significant changes in bilirubin

    Change from baseline

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

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

    Millimeter of mercury (mmHg)

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

  6. Incidence of clinically significant changes in vital sign - Pulse rate

    Beats per minute (BPM)

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

  7. Incidence of clinically significant changes in vital sign - Body Temperature

    Celsius (°C)

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

  8. Incidence of clinically significant changes in vital signs - Weight

    Kilograms (kg)

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

  9. Incidence of clinically significant changes in ECGs

    QT interval (milli second (ms))

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

Secondary outcomes (2)
  1. Preliminary efficacy by means of RECIST evaluation

    1. ORR will be assessed by monitoring tumor response and progression using RECIST v1.1
    2. ORR will be assessed by monitoring tumor response and progression using mRECIST
    3. ORR will be assessed by monitoring tumor response and progression using RECIST v 1.1 in liver lesions only

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

  2. Plasma levels of α fetoprotein (AFP)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Dec 2018
  2. Study start5 Sep 2018
  3. Primary completion7 Jan 2025
  4. Study completion16 Jun 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Intrapatient dose escalations continuing into interpatient dose escalations to end with dose expansion cohorts.
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03781934
Sponsor's protocol ID
MIV-818-101/201
Status last verified
Jun 2025
First submitted
7 Nov 2018
Last updated
1 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing MIV-818 (fostroxacitabine bralpamide) + pembrolizumab and MIV-818 (fostroxacitabine bralpamide) + lenvatinib in people with Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma, run by Medivir at 18 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in South Korea, Spain, United Kingdom, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and Severity of Adverse Events (AEs) (time frame: Participants monitored throughout treatment period and during follow-up, up to 6 months). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2025.

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