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Hepatocellular CarcinomaPhase 1Liver-NET1NCT05546879

Study Investigating the Association of NP137 With Atezolizumab-Bevacizumab Combination in First Line in Unresectable HCC

A Phase 1 study testing NP137, Atezolizumab and Bevacizumab in people with Hepatocellular Carcinoma, run by University Hospital, Grenoble at 9 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The study will assess the safety of the association of NP137 with the standard of care Atezolizumab-Bevacizumab in first line setting in patients with unresectable hepatocellular carcinoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
NP137, Atezolizumab and Bevacizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
9 sitesFrance
Study dates
15 Mar 2023to 19 Mar 2029
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • Males or females ≥ 18 years of age
  • Histologically confirmed (liver biopsy within 24 previous weeks) and documented unresectable hepatocellular carcinoma
  • Patients with a BCLC C or BCLC B status ineligible for or in failure of locoregional treatment, as per the Barcelona Clinic Liver Cancer (BCLC) staging system
  • No prior systemic therapy for advanced HCC
  • Liver tumor burden \< 50% of the liver (per Investigator judgment)
  • Child-Pugh A (≤ 6) without any history of cirrhotic decompensation within the past 6 months
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  • Antiviral therapy required in hepatitis B virus patients (Hepatitis B antigen positive)
  • Willing to have liver biopsy between C4 and C5
  • Presence of a measurable tumor per RECIST v1.1 criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  • Life expectancy ≥ 12 weeks
  • Absence of previous liver decompensation
  • In case of cirrhosis, last esophageal varices detection by esogastroduodenal endoscopy have to be performed within last the 6 months before inclusion
  • Adequate hematologic function prior to the first dose of NP137, defined as:
  • Absolute neutrophils count ≥ 1500 cells/μL 14.2. Hemoglobin ≥ 9 g/dL with no transfusion within 4 weeks prior to first planned dose of NP137 14.3. Platelet count \> 50,000/μL with no transfusion within 2 weeks prior to first planned dose of NP137
  • Adequate renal function prior to first dose, defined as:
  • 15.1. Serum creatinine \< 1.5 × Upper limit of normal (ULN ) 15.2. Creatinine clearance ≥ 30 mL/min/m2 (by Cockroft-Gault equation of 24-hour urine) if creatinine ≥ 1.5 × ULN
  • Adequate hepatic function prior first dose, defined as AST/ALT ≤ 5 × ULN
  • Women patients of childbearing potential must have a negative serum pregnancy test at screening and baseline, and be willing to use a highly effective contraception. The patient should be advised to continue the contraception for at least 6 months following the completion of dosing. Women with cessation for \> 24 months of previously occurring menses, or women of any age who have had a hysterectomy, or have had both ovaries removed will be considered to be of non-childbearing potential.
  • Male patients of reproductive potential must be willing to use one acceptable method of contraception, as judged by Investigator and Sponsor and/or to refrain from donating sperm from the time of screening through at least 6 months following the completion of dose administration.
  • Amenable to computed tomography (CT) with 3 or 4 phase liver or magnetic resonance imaging (MRI) of abdomen and pelvis, and CT of chest, or MRI of whole body, for initial tumor size measurements and subsequent follow-up.
  • Absence of other clinically relevant abnormalities for any screening laboratory test results as judged by the Investigator and Sponsor.
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Able to understand and provide written informed consent
  • Patients covered by Health Insurance System

Who cannot join

  • Any known history of encephalopathy within 6 months prior to first planned dose of treatment
  • Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding
  • Known esophageal varices with recent history of bleeding (within previous 6 months)
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
  • Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
  • Chronic treatment with immunosuppressive agents (like steroids) ≤ 6 weeks prior to first planned dose of treatment.
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  • Major surgical procedures, open biopsy or significant traumatic injury ≤ 4 weeks prior to first dose of treatment or anticipation of major surgical procedure during the course of the trial, minor surgical procedures ≤ 1 week of first planned dose (the surgical wound must be fully healed)
  • Local therapy to liver within 28 days prior to initiation of study treatment or non-recovery from side effects of any such procedure
  • Any clinically significant cardiovascular condition as judged by the Investigator (such as New York Heart Association Class II or greater cardiac failure, myocardial infarction, or cerebrovascular accident within 3 months prior to Day 1 of Cycle 1, uncontrolled arterial hypertension, unstable arrhythmia, or unstable angina)
  • Severe or uncontrolled renal condition
  • Untreated chronic hepatitis B
  • Co-infection of HBV and HCV
  • Use of any prohibited concomitant medications within 14 days of the Baseline/Day 1 visit
  • Contraindication to additionnal liver biopsy planned between C4 and C5
  • Contraindication to iodinated contrast agent infusion
  • Known current alcohol (\> 20g/ Day in women and \> 30g/ Day in men) or substance abuse
  • History of leptomeningeal disease
  • Active or history of autoimmune disease or immune deficiency
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
  • Known active tuberculosis
  • History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
  • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 6 months after the last dose of treatment
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
  • Uncontrolled tumor-related pain
  • Uncontrolled or symptomatic hypercalcemia
  • Treatment with systemic immunostimulatory agents
  • Inadequately controlled arterial hypertension
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • Evidence of bleeding diathesis or significant coagulopathy
  • History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or requirement for routine parenteral hydration
  • Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
  • Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses
  • Known clinically significant or life threatening organ or systemic disease such that in the opinion of the Investigator, the significance of the disease will compromise the patient\'s participation in the trial
  • Known intolerance or hypersensitivity to the active ingredient or to one of the components of the study drug
  • Persistent toxicities related to prior treatment of grade greater than 1
  • Subjects with active infection
  • History of bone marrow allograft or solid organ transplant
  • Subjects requiring corticosteroid therapy at a dose equivalent to more than 10 mg of prednisone equivalent dose per day (corticosteroid administration is permitted by a route resulting in minimal systemic exposure [cutaneous, rectal, articular, ocular or inhalation] is authorized).
  • Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies
  • History of gastrointestinal perforations and fistulae
  • Uncontrolled or symptomatic proteinuria
  • Active aneurysm considered as unstable and/or at high risk of complication
  • Patients who experienced immune-mediated pericardial disorders during previous treatment by immune checkpoint blockade therapies, including anti-CTLA4, anti-PD1, and anti-PDL1 therapeutic antibodies
  • Subject who participate or plan to participate in another interventional clinical trial or who is in exclusion period for another study,
  • Subject who cannot be contacted in case of emergency
  • Persons referred to in Articles L1121-5 to L1121-8 of the French code of public health (this corresponds to all persons protected: pregnant or parturient women, breastfeeding mothers, persons deprived of liberty by judicial or administrative decision, persons subject to a legal protection measure).

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

France9 sites

  • CHU Angers

    Angers

  • Hôpital Haut Lêveque

    Bordeaux

  • CHU de GRENOBLE ALPES

    Grenoble, Alpes, 38043

  • 12 Hôpital St Joseph

    Marseille

  • CHU Nantes

    Nantes

  • AP-HP Beaujon

    Paris

  • AP-HP St Antoine

    Paris

  • CHU Reims

    Reims

  • CHU Toulouse

    Toulouse

Other trials in France

About this study

Official title: Study Investigating the Association of NP137 With Atezolizumab-Bevacizumab Combination in First Line in Unresectable Hepatocellular Carcinoma

The study will assess the safety of the association of NP137 with the standard of care Atezolizumab-Bevacizumab in first line setting in patients with unresectable hepatocellular carcinoma. The study drug which is tested is the NP137 in association with Atezolizumab-Bevacizumab to allow a better tumor response as well as better survival outcomes with an acceptable safety.

Read the detailed description

The study is a multicentric, prospective, single arm phase 1b trial. This study will enroll 43 to 52 patients and consists of 2 parts: Safety Lead-in Phase and Expansion Phase. Initially, 3 to 12 patients will be enrolled into a Safety Lead-in Phase based on a 3 + 3 design, with the possibility of dose de-escalation, to confirm the recommended dose of NP137.

The Expansion Phase will start after completion of Safety Lead-in Phase at the confirmed dose and will include 40 patients. Patients will be assigned to the experimental single arm (NP137+ Atezolizumab-Bevacizumab).

Being tested
NP137, Atezolizumab, Bevacizumab
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • NP137Drug

    NP137 at 9 or 14 mg/kg IV will be administered every 21 days.

  • AtezolizumabDrug

    Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-days cycle

  • BevacizumabDrug

    Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle

Study groups in NCT05546879
Study groupRoleWhat they receive
ExperimentalExperimentalNP137+Atezolizumab-Bevacizumab
Receives: Drug: NP137; Drug: Atezolizumab; Drug: Bevacizumab

What is being measured

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

  1. Percentage Proportion of patients experiencing adverse events

    Percentage Proportion of patients experiencing adverse events (AEs) of any grade and grade 3/4 AEs as defined by the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE v 5.0) throughout the study period.

    Measured: At 36 months

Secondary outcomes (9)

  1. Best overall objective response rate (ORR)

    Best overall objective response rate (ORR) and ORR at 3 months, 6, 9, 12 months according to mRECIST and RECIST 1.1.

    Measured: At 36 months

  2. Overall survival (OS)

    Median Overall survival (OS) at 6, 12, 18, 24 and 36 months-OS rates. OS is defined as the time between the first administration of the association NP137 + Atezolizumab-Bevacizumab and death (all causes). Patients alive will be censored at the date of last news.

    Measured: At 36 months

  3. Progression-Free Survival (PFS)

    Median Progression-Free Survival (PFS), 6, 12, 18, 24 and 36 months-PFS rates according to RECIST 1.1. PFS is defined as the time between the first administration of the association NP137 + Atezolizumab-Bevacizumab and progression according to RECIST 1.1 or death (all causes). Patients alive without progression will be censored at the date of last news.

    Measured: At 36 months

  4. Duration of response

    Median Duration of response is defined as the time between onset of response (first PR or CR status) and progression according to RECIST 1.1. Patients alive without progression will be censored at the date of last news.

    Measured: At 36 months

  5. Alpha-fetoprotein (AFP) response

    AFP response will be defined as a percentage of patients with a ≥ 50% reduction from baseline AFP level, at 3, 6, 12 months

    Measured: At 36 months

  6. Quality of life (QoL)

    QoL will be studied by using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire for Cancer at baseline, 3, 6, 12 months. A 5-point decrease of QLQ-C30 score will be considered as the minimal clinically significant deterioration of QoL.

    Measured: At 36 months

  7. time to deterioration (TTD)

    TTD will be defined as the time from inclusion in the study to deterioration of EORTC QLQ-C30 score with a decrease ≥5 points at any time point after the baseline score at 6 months and at the end of study.

    Measured: At 36 months

  8. PK-PD evaluation

    based on available PopPK modelisation and PK samples collected at the time of the response evaluation in this study

    Measured: At 36 months

  9. Mechanism of EMT

    To assess the mechanisms of EMT reversal by comparing different histological markers on pre-therapeutic and Cycle4-Cycle5 biopsies. Descriptive study in transcriptomics and immunohistochemistry of the evolution of EMT markers, the expression of Netrin-1 and its receptors, and tumor microenvironment during treatment by comparing pre-therapeutic biopsies to Cycle4-Cycle5 biopsies

    Measured: At 36 months

Timeline

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

  1. First posted21 Sep 2022
  2. Study start15 Mar 2023
  3. Primary completion19 Mar 2026
  4. Study completion19 Mar 2029 (estimated)

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Multicentric prospective single arm phase 1b trial
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05546879
Sponsor's protocol ID
38RC22.210
Acronym
Liver-NET1
Status last verified
May 2026
First submitted
15 Sep 2022
Last updated
20 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing NP137, Atezolizumab and Bevacizumab in people with Hepatocellular Carcinoma, run by University Hospital, Grenoble at 9 sites in France.

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 25 inclusion and 46 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: under way, not looking for participants, as of the sponsor's last update on 20 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in France. 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 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.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Percentage Proportion of patients experiencing adverse events (time frame: At 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05546879.

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 20 May 2026.

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