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

NCT05546879 | Suspended Phase 1 DMC

• 1 other identifier: 38RC22.210
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief 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.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.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (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.

  At 36 months

Secondary Outcomes (9)

• Best overall objective response rate (ORR)

  At 36 months

• Overall survival (OS)

  At 36 months

• Progression-Free Survival (PFS)

  At 36 months

• Duration of response

  At 36 months

• Alpha-fetoprotein (AFP) response

  At 36 months

Study Arms (1)

Experimental

EXPERIMENTAL

NP137+Atezolizumab-Bevacizumab

Drug: NP137; Drug: Atezolizumab; Drug: Bevacizumab

Interventions

NP137 DRUG

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

Experimental

Atezolizumab DRUG

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

Experimental

Bevacizumab DRUG

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

Experimental

Eligibility Criteria

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

You may qualify if:

• 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
• 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
• 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:

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• University Hospital, Grenoble: lead
• NETRIS Pharma: collaborator

Study Sites (1)

CHU de GRENOBLE ALPES

Grenoble, Alpes, 38043, France

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

netrin-1 inhibitor NP137; atezolizumab; Bevacizumab

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Gaël ROTH, MD PHD

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicentric prospective single arm phase 1b trial

Study Record Dates

• First Submitted: September 15, 2022
• First Posted: September 21, 2022
• Study Start: March 15, 2023
• Primary Completion: March 15, 2026
• Study Completion (Estimated): March 15, 2027
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)