LIVMONIPLIMAB for Hepatocellular carcinoma (locally advanced or metastatic) | Hepatocellular carcinoma (metastatic)

Inclusion criteria

• {"criterion_text":"- Subjects or their legally authorized representative must voluntarily sign and date an informed consent, approved by an IEC/IRB, prior to the initiation of any screening or study-specific procedures.\n- Subjects with HBV infection will be allowed to enroll if they meet the following criteria: HBV DNA < 500 IU/mL obtained within 35 days prior to initiation of study treatment, eatment for the study duration and for at least 6 months after the last dose of study drug.AND Anti-HBV treatment (per local standard of care) for a minimum of 14 days prior to first dose and willingness to continue tr\n- Subjects with resolved HBV infection (HBsAg-negative, HBcAb-positive) are eligible if they are willing to comply with HBV DNA monitoring while on study drug and agree to initiate antiviral therapy if HBV DNA becomes detectable (≥ 10 IU/mL or above the limit of detection). Subjects with a negative HBcAb and positive HBsAb at screening must agree to comply with HBV DNA monitoring if they have no prior history of receiving a complete hepatitis B vaccination series or where locally mandated.\n- No history or current Grade ≥ 3/major immunologic reactions to any IgG-containing agent/mAb.\n- Eligible to enroll:Vitiligo or alopecia. Hypothyroidism stable on hormone rNo active or prior documented history of autoimmune, immune deficiency, or inflammatory disorders including, but not limited to, inflammatory bowel disease, systemic lupus erythematosus, sarcoidosis, Wegener syndrome, rheumatoid arthritis, antiphospholipid antibody syndrome, Guillain-Barre syndrome, or multiple sclerosis. The following are exceptions to this criterion and subjects with these conditions are eleplacement. ·\tAny chronic skin condition that does not require systemic therapy. ·\tCeliac disease controlled by diet alone. ·\tType 1 diabetes on an insulin regimen. Controlled HIV. Subjects infected with HIV may be enrolled if the following criteria are met: CD4 count is ≥ 100 cells/ tL. (If CD4 count is < 200 cells/ tL, a CD4 to CD8 ratio > 0.4 is required.) Subject has been receiving effective ART for at least 4 weeks with an HIV viral load of less than 200 copies/mL, and subject has no symptomatic AEs higher than Grade 1 attributed to ART.\n- No known active SARS-CoV-2 infection. If a subject has signs/symptoms suggestive of SARS-CoV-2 infection, the subject must have a negative molecular (e.g., PCR) test or 2 negative antigen test results at least 24 hours apart. Note: SARSCoV-2 diagnostic tests should be applied following local requirements/recommendations. mptoms.Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be screen failed and may only rescreen for the study after they meet the following SARS-CoV-2 infection viral clearance criteria: At least 10 days since first positive test result have passed in asymptomatic patients or at least 10 days since recovery, defined as resolution of fever without use of antipyretics and improvement in sy\n- No history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.\n- No history of clinically significant conditions within the last 6 months (unless otherwise noted) that in the investigator's opinion, would adversely affect the subject's participation in the study including, but not limited to, the following: ·\tGrade ≥ 2 peripheral neuropathy (unrelated to prior anticancer therapy). ·\tSymptomatic congestive heart failure (NYHA class > 2). ·\tUnstable angina pectoris or cardiac arrhythmia (NYHA class > 2). ·\tArterial hypertension (defined as systolic BP ≥ 150 mmHg and/or diastolic BP ≥ 100 mmHg), based on an average of ≥ 3 BP readings on ≥ 2 sessions. Anti-hypertensive therapy to achieve these parameters is allowable. ·\tVascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to initiation of study treatment. No evidence of bleeding diathesis or significant coagulopathy. ·\tIdiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis. ·\tPleural effusion or pericardial effusion requiring recurrent drainage procedures (once monthly or more frequently).\n- No history of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months.\n- Subjects must be ≥ 18 years old at time of signing ICF and must weigh ≥ 35 kg.\n- Laboratory values must meet the following criteria within the screening period prior to the first dose of study drug: ·\tHemoglobin ≥ 8.0 g/dL. ·\tAbsolute neutrophil count ≥ 1000/mm3. ·\tPlatelet count ≥ 75,000/mm3. ·\tALT and AST ≤ 5 × ULN. ·\tTotal bilirubin ≤ 2 mg/dL. Mildly elevated total bilirubin (< 4mg/dL) is allowed if Gilbert's syndrome is documented and the direct bilirubin is ≤ 2 mg/dL. ·\tCreatinine clearance ≥ 40 mL/min based on Cockcroft-Gault glomerular filtration rate estimation. ·\tAlbumin ≥ 2.8 g/L. ·\tLipase ≤ 2 × ULN. ·\tINR ≤ 1.6. ·\tUrine protein < 2+ on screening urinalysis. Subjects with 2+ or greater proteinuria should undergo a 24-hour urine collection and must demonstrate < 1 g of protein in 24 hours.\n- Are willing and able to comply with procedures required in this protocol.\n- Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology or cytology or clinically by American Association for the Study of Liver Diseases criteria for patients with cirrhosis. Subjects with fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma/HCC are not eligible to enroll.\n- BCLC Stage B or C.\n- Disease that is not amenable to surgical and/or locoregional therapies. Subjects with progressive disease after surgical and/or locoregional therapy may enroll if the disease is no longer amenable to surgical or locoregional therapy. For subjects who progressed after locoregional therapy for HCC, locoregional therapy must have been completed ≥ 28 days prior to baseline scan for the current study.\n- No prior systemic therapy for HCC including chemotherapy, immunotherapy, biologic therapy, hormonal therapy, herbal therapy, or investigational agents. Use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is allowed.\n- Must have at least one measurable HCC lesion based on RECIST 1.1 as determined by the local site investigator/radiology assessment. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions."}

Exclusion criteria

• {"criterion_text":"- For all females of child-bearing potential; a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at C1D1 prior to the first dose of study drug.\n- No history of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.\n- No known hypersensitivity to Chinese hamster ovary cell products or to any component of the budigalimab or livmoniplimab formulation.\n- Subject must not have been treated with any investigational drug within 30 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of study drug or is currently enrolled in another clinical study or was previously enrolled in this study.\n- Female subjects of childbearing potential must practice at least 1 protocol-specified method of birth control, that is effective from Study Day 1 through at least 5 months after the last dose of study drug. Persons of non-childbearing potential do not need to use birth control.\n- Female subjects who are not pregnant or breastfeeding, and are not considering becoming pregnant or donating eggs/sperm during the study and for at least 5 months after the last dose of study drug.\n- If male, and subject is sexually active with female partner(s) of childbearing potential, he must agree, from Study Day 1 through 5 months after the last dose of study drug, to practice the protocol-specified contraception.\n- Male who is not considering fathering a child or donating sperm during the study and for approximately 5 months after the last dose of study drug.\n- No treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics are eligible for the study.\n- No current or prior use of immunosuppressive medication within 14 days before the first dose of study drug(s)The following are exceptions to this criterion:Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection).Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.Steroids as premedication for hypersensitivity reactions (e.g.,CT scan premedication).\n- No prior therapy with any agent that targets the TGF-β signaling pathway.\n- No known hypersensitivity to CTLA4 or PD-1/PD-L1 targeting agents."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint for Stage 1 is the BOR of CR/PR per RECIST 1.1 by investigator.","definition_or_measurement_approach":"BOR (best overall response) of CR/PR assessed per RECIST 1.1 by investigator assessment."}
• {"endpoint_text":"- The primary endpoint for Stage 2 is OS.","definition_or_measurement_approach":"Overall survival (OS) measured as time from randomization to death from any cause."}

Secondary endpoints

• {"endpoint_text":"- The secondary endpoints for Stage 1 are PFS, DoR per RECIST 1.1 by investigator, OS, safety and tolerability, and PK assessments.","definition_or_measurement_approach":"PFS (progression-free survival), DoR (duration of response) assessed per RECIST 1.1 by investigator; OS; safety/tolerability assessments; pharmacokinetics (PK) assessments."}
• {"endpoint_text":"- The secondary endpoints for Stage 2 are PFS, BOR of CR/PR, and DOR per RECIST 1.1 by BICR and by investigator, PFS, BOR of CR/PR and DoR per iRECIST by BICR and by investigator; and PROs.","definition_or_measurement_approach":"PFS, BOR of CR/PR, DoR assessed per RECIST 1.1 and iRECIST by both blinded independent central review (BICR) and investigator; patient-reported outcomes (PROs)."}

Methods

• Third-party recruitment support contracted to Massive Bio Inc. (duty labelled as 'recruitment' in sponsor third-party listing).
• Site-based recruitment via participating hospital/clinic oncology departments at listed investigational sites in Italy, Spain and France (standard site recruitment procedures implied by site participation).
• Recruitment arrangements and memos exist (e.g., country-specific recruitment documents listed) but details of channels (advertising, registries, social media) are not provided in the available data.

Italy

Earliest CTIS Part Ii Submission Date

24-04-2024

Latest Decision Or Authorization Date

24-07-2025

Processing Time Days

456

Number Of Sites

8

Number Of Participants

10

Spain

Earliest CTIS Part Ii Submission Date

26-04-2024

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

570

Number Of Sites

8

Number Of Participants

17

France

Earliest CTIS Part Ii Submission Date

26-04-2024

Latest Decision Or Authorization Date

05-03-2026

Processing Time Days

678

Number Of Sites

4

Number Of Participants

13

Primary sponsor

Full Name

AbbVie Deutschland GmbH & Co. KG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

Endpoint Clinical Inc.

Responsibilities

sponsorDuties code: 3 (clinical operations/CRO functions as indicated in third-party listing)

Third parties

• {"country":"United States","full_name":"Canopy Biosciences LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"sponsorDuties codes: [3]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Mosaic Laboratories LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Massive Bio Inc.","duties_or_roles":"sponsorDuties code: [15]; value: recruitment","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties code: [15]; value: eCOA","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"sponsorDuties code: [15]; value: DMC","organisation_type":"Non-Pharmaceutical company"}