Locally Advanced or Metastatic Hepatocellular Carcinoma: Dose Optimization, Safety, and Efficacy of Livmoniplimab in Combination with Budigalimab in Subjects Who Have Not Previously Received Systemic Treatment – LIVIGNO-2

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

9 May 2024 → ongoing

Decision date (initial)

2024-04-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Abbvie Inc

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective for Stage 1 (Phase 2) is to select the optimal livmoniplimab dose in combination with budigalimab for the Phase 3 study in subjects with locally advanced or metastatic HCC who have not previously received systemic treatment for HCC.
The primary objective for Stage 2 (Phase 3) is to evaluate the efficacy of the livmoniplimab and budigalimab combination as measured by OS in subjects with locally advanced or metastatic HCC who have not previously received systemic treatment for HCC.

Secondary objectives 3

1. Stage 1 and Stage 2: To assess the safety, tolerability, immunogenicity, and pharmacokinetics (PK) of livmoniplimab in combination with budigalimab.
2. Stage 2: To evaluate the efficacy of livmoniplimab in combination with budigalimab as measured by progression-free survival (PFS), best overall response (BOR) of complete response (CR)/partial response (PR), and duration of response (DoR).
3. Stage 2: To assess the impact of livmoniplimab in combination with budigalimab on patient-reported outcomes (PROs).

Conditions and MedDRA coding

Metastatic Hepatocellular Carcinoma (HCC)

Regulatory references

Scientific advice from competent authorities

AbbVie Biotechnology GmbH

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information. To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/ For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. 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.
2. Subjects must be ≥ 18 years old at time of signing ICF and must weigh ≥ 35 kg.
3. Laboratory values must meet the following criteria within the screening period prior to the first dose of study drug: · Hemoglobin ≥ 8.0 g/dL. · Absolute neutrophil count ≥ 1000/mm3. · Platelet count ≥ 75,000/mm3. · ALT and AST ≤ 5 × ULN. · Total 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. · Creatinine clearance ≥ 40 mL/min based on Cockcroft-Gault glomerular filtration rate estimation. · Albumin ≥ 2.8 g/L. · Lipase ≤ 2 × ULN. · INR ≤ 1.6. · Urine 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.
4. Are willing and able to comply with procedures required in this protocol.
5. 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.
6. BCLC Stage B or C.
7. 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.
8. 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.
9. 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.
10. 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
11. 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.
12. No history or current Grade ≥ 3/major immunologic reactions to any IgG-containing agent/mAb.
13. 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. · Any chronic skin condition that does not require systemic therapy. · Celiac disease controlled by diet alone. · Type 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.
14. 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
15. 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.
16. 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: · Grade ≥ 2 peripheral neuropathy (unrelated to prior anticancer therapy). · Symptomatic congestive heart failure (NYHA class > 2). · Unstable angina pectoris or cardiac arrhythmia (NYHA class > 2). · Arterial 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. · Vascular 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. · Idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis. · Pleural effusion or pericardial effusion requiring recurrent drainage procedures (once monthly or more frequently).
17. No history of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months.

Exclusion criteria 12

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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).
8. No prior therapy with any agent that targets the TGF-β signaling pathway.
9. No known hypersensitivity to CTLA4 or PD-1/PD-L1 targeting agents.
10. No history of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
11. No known hypersensitivity to Chinese hamster ovary cell products or to any component of the budigalimab or livmoniplimab formulation.
12. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The primary endpoint for Stage 1 is the BOR of CR/PR per RECIST 1.1 by investigator.
2. The primary endpoint for Stage 2 is OS.

Secondary endpoints 2

1. The secondary endpoints for Stage 1 are PFS, DoR per RECIST 1.1 by investigator, OS, safety and tolerability, and PK assessments.
2. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation

AbbVie Deutschland GmbH & Co. KG

Address

Mainzer Strasse 81

City

Wiesbaden

Postcode

65189

Country

Germany

Scientific contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 8

Locations

3 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 25 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications