Livmoniplimab + Budigalimab for Liver Cancer

(LIVIGNO-2 Trial)

Recruiting at 45 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: AbbVie

Disqualifiers: Prior systemic therapy, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

660 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for advanced liver cancer, specifically hepatocellular carcinoma (HCC). The researchers aim to determine the optimal dose and assess the effects and safety of two new drugs, livmoniplimab (a human monoclonal antibody) and budigalimab (also known as ABBV-181), either together or compared to other treatments. Participants will receive these treatments to evaluate their effectiveness in managing the cancer. The trial seeks individuals with advanced liver cancer that cannot be surgically removed. Participants must not have received previous treatments for their liver cancer. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potential advancements in liver cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining livmoniplimab with budigalimab is generally safe for patients. One study on this combination found it safe, with manageable side effects. Budigalimab has been well-tolerated in other studies, showing positive results in people with advanced tumors. These findings suggest that the treatments in this trial are likely safe for most participants, with side effects manageable with medical help. Prospective participants should discuss any concerns with their doctor before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Livmoniplimab and Budigalimab for liver cancer because these treatments work differently from current options. Most existing therapies, like sorafenib or lenvatinib, target specific enzymes involved in tumor growth. However, Livmoniplimab and Budigalimab are monoclonal antibodies that enhance the body's immune response, potentially leading to more effective tumor eradication. This immunotherapy approach offers hope for patients by possibly providing longer-lasting remissions compared to traditional treatments.

What evidence suggests that this trial's treatments could be effective for liver cancer?

This trial will evaluate different treatments for liver cancer. A previous study showed that livmoniplimab, when combined with another treatment, achieved a 42% overall response rate in liver cancer patients, indicating nearly half experienced tumor reduction. Budigalimab, used with another drug, also produced better results in patients with advanced cancers. In this trial, some participants will receive a combination of livmoniplimab and budigalimab, which might be effective due to their different mechanisms of attacking cancer cells. Early research suggests this combination could be promising for treating liver cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with advanced liver cancer (HCC) that can't be surgically removed or has spread, confirmed by tests or clinical criteria. They should have a certain level of liver function (Child-Pugh A or B7) and be able to perform daily activities with little to no assistance (ECOG 0-1).

Inclusion Criteria

I am fully active or can carry out light work.

My liver cancer cannot be removed by surgery and is confirmed by tests or clinical criteria.

My liver cancer is at an intermediate or advanced stage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Stage 1

Participants receive treatment in one of three arms: livmoniplimab with budigalimab, atezolizumab with bevacizumab, or tremelimumab with durvalumab. Treatment is administered every 3 or 4 weeks depending on the arm.

Until disease progression or discontinuation criteria are met

Regular visits every 3-4 weeks

Treatment - Stage 2

Participants receive treatment in one of two arms: livmoniplimab with budigalimab or tremelimumab with durvalumab. Treatment is administered every 3 or 4 weeks depending on the arm.

Until disease progression or discontinuation criteria are met

Regular visits every 3-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Budigalimab
• Livmoniplimab

Trial Overview The trial is testing different doses of Livmoniplimab combined with Budigalimab against other treatments like Atezolizumab/Bevacizumab and Tremelimumab/Durvalumab in adults with HCC. Participants are randomly assigned to these groups and treated every few weeks until disease progression.

How Is the Trial Designed?

Group I: Stage 2: Arm 1 Experimental Treatment 2 Interventions

Participants will receive livmoniplimab (optimized dose) in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.

Group II: Stage 1: Cohort 2 Experimental Treatment 2 Interventions

Participants will receive livmoniplimab Dose 2 in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.

Group III: Stage 1: Cohort 1 Experimental Treatment 2 Interventions

Participants will receive livmoniplimab Dose 1 in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.

Group IV: Stage 2: Arm 2 (Control) Active Control 2 Interventions

Participants will receive a single dose of tremelimumab in combination with durvalumab every 4 weeks until disease progression or until discontinuation criteria are met.

Group V: Stage 1: Cohort 3 - Group 1 (Control) Active Control 2 Interventions

Participants will receive atezolizumab in combination with bevacizumab every 3 weeks until disease progression or until discontinuation criteria are met.

Group VI: Stage 1: Cohort 3 - Group 2 (Control) Active Control 2 Interventions

Participants will receive a single dose of tremelimumab in combination with durvalumab every four weeks until disease progression or until discontinuation criteria are met.

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

M2BPGi is a promising serum marker for diagnosing liver fibrosis in chronic liver diseases, including chronic hepatitis B and C, and nonalcoholic fatty liver disease (NAFLD).

M2BPGi not only predicts liver fibrosis but also helps assess the risk of hepatocellular carcinoma (HCC) and liver function in patients, indicating its potential role in monitoring disease progression and treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Utility of Mac-2 Binding Protein Glycosylation Isomer in Chronic Liver Diseases. Tamaki, N., Kurosaki, M., Loomba, R., et al.[2021]

In a study of 899 chronic hepatitis B patients on long-term entecavir therapy, higher levels of the biomarker M2BPGi were significantly associated with an increased risk of developing hepatocellular carcinoma (HCC), with a hazard ratio of 5.80 for those in the high M2BPGi group.

M2BPGi levels can enhance the predictive accuracy of the PAGE-B score, a well-established model for assessing HCC risk, particularly in patients with intermediate PAGE-B scores, indicating its potential as a valuable tool in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline Mac-2 Binding Protein Glycosylation Isomer Level Stratifies Risks of Hepatocellular Carcinoma in Chronic Hepatitis B Patients with Oral Antiviral Therapy. Tseng, TC., Peng, CY., Hsu, YC., et al.[2022]

In a phase I/II study involving 219 patients with advanced solid tumors, the combination of sabatolimab and spartalizumab was well tolerated, with fatigue being the most common treatment-related side effect.

While no responses were observed with sabatolimab alone, the combination treatment showed preliminary antitumor activity, with 5 patients achieving partial responses in various cancers, suggesting potential efficacy in specific populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/Ib Clinical Trial of Sabatolimab, an Anti-TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti-PD-1 Antibody, in Advanced Solid Tumors. Curigliano, G., Gelderblom, H., Mach, N., et al.[2023]

Budigalimab, a monoclonal antibody targeting PD-1, demonstrated a safety profile similar to other PD-1 inhibitors, with the most common severe side effect being anemia in 22% of HNSCC patients and 13% of NSCLC patients.

In terms of efficacy, budigalimab showed objective response rates of 13% in head and neck squamous cell carcinoma (HNSCC) and 19% in non-small cell lung cancer (NSCLC), with median progression-free survival of 3.6 months and 1.9 months, respectively, indicating it may be a viable treatment option for these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human phase 1 study of budigalimab, an anti-PD-1 inhibitor, in patients with non-small cell lung cancer and head and neck squamous cell carcinoma. Italiano, A., Cassier, PA., Lin, CC., et al.[2023]

M2BPGi is identified as a strong short-term predictor of hepatocellular carcinoma (HCC) in untreated chronic hepatitis B patients, with a significant odds ratio of 7.40 for predicting HCC within 1-2 years for those with elevated levels.

In a study of 1070 samples, M2BPGi, along with α-fetoprotein (AFP) and hepatitis B surface antigen (HBsAg), were found to be independent predictors of HCC, demonstrating the potential of M2BPGi in early detection of this cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum Levels of M2BPGi as Short-Term Predictors of Hepatocellular Carcinoma in Untreated Chronic Hepatitis B Patients. Liu, J., Hu, HH., Lee, MH., et al.[2019]

In a study of 100 hepatocellular carcinoma (HCC) cases matched with 185 chronic hepatitis B (CHB) patients receiving entecavir treatment, higher serum levels of Mac-2-binding protein glycosylation isomer (M2BPGi) were significantly associated with the development of HCC, indicating its potential as a predictive biomarker.

Baseline serum M2BPGi levels were identified as the only independent factor linked to incident HCC, with a cut-off value of 1.15 COI showing high sensitivity (90%) for predicting HCC in cirrhotic patients, suggesting its utility in identifying high-risk individuals during antiviral treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum Mac-2-binding protein glycosylation isomer and risk of hepatocellular carcinoma in entecavir-treated chronic hepatitis B patients. Mak, LY., Ko, M., To, E., et al.[2020]

In a study of 147 chronic hepatitis B patients undergoing nucleoside analogue therapy, serum levels of the fibrosis marker M2BPGi significantly decreased over time, indicating a potential response to treatment.

High serum M2BPGi levels at 48 weeks were identified as a strong independent risk factor for developing hepatocellular carcinoma, with a cutoff value of >1.5 correlating to a 34.9 times higher risk, highlighting its predictive value for HCC in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

On-treatment Serum Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Level and Risk of Hepatocellular Carcinoma Development in Patients with Chronic Hepatitis B during Nucleot(s)ide Analogue Therapy. Murata, A., Amano, N., Sato, S., et al.[2020]

Abagovomab, an anti-idiotypic antibody targeting CA-125, was found to be safe and well tolerated in a phase I trial with 36 patients, showing no treatment-limiting toxicities and only mild local injection site reactions.

The longer vaccination schedule (nine injections) led to a higher frequency of CA-125 specific CD8+ T-cells and successful induction of immune responses in all evaluable patients, suggesting it may be more effective than the shorter schedule.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer. A phase I trial of the AGO-OVAR. Pfisterer, J., du Bois, A., Sehouli, J., et al.[2020]

Tremelimumab, an immune checkpoint inhibitor targeting CTLA-4, can lead to significant tumor shrinkage in solid tumors, even after initial rapid disease progression, as seen in two case studies involving bile duct cancer and squamous cell carcinoma.

Remarkably, these responses occurred without any immune-related adverse events, indicating a potentially safe profile for tremelimumab in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremelimumab-associated tumor regression following after initial progression: two case reports. Shimomura, A., Fujiwara, Y., Kondo, S., et al.[2019]

The combination of nivolumab (10 mg/kg) with standard chemotherapy was well tolerated in patients with advanced non-small-cell lung cancer (NSCLC), with only one case of dose-limiting toxicity observed among 24 patients across four treatment arms.

Nivolumab combined with chemotherapy showed promising antitumor activity, with median progression-free survival ranging from 3.15 months to 9.63 months, indicating its potential effectiveness in treating advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study. Kanda, S., Goto, K., Shiraishi, H., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS4190

Phase 2/3 study of livmoniplimab in combination with ... A phase 1 study in HCC showed an overall response rate (ORR) of 42% (5/12) when combining livmoniplimab with the programmed cell death 1 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06109272

NCT06109272 | A Study to Assess the Dose, Adverse ... The purpose of this study is to evaluate the optimized dose, adverse events, and efficacy of livmoniplimab in combination with budigalimab. Livmoniplimab is an ...

3. onclive.com onclive.com/view/budigalimab-plus-abbv-151-demonstrates-variable-activity-across-locally-advanced-or-metastatic-solid-tumors

Budigalimab Plus ABBV-151 Demonstrates Variable ... The addition of budigalimab to ABBV-151 was well tolerated and significantly enhanced responses in patients with locally advanced or metastatic solid tumors.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06487559

NCT06487559 | A Study to Assess the Adverse Events and ... The purpose of this study is to assess adverse events and how livmoniplimab in combination with budigalimab moves through the body in adult Chinese participants ...

5. researchgate.net researchgate.net/publication/381979970_Phase_23_study_of_livmoniplimab_in_combination_with_budigalimab_in_patients_with_locally_advanced_or_metastatic_hepatocellular_carcinoma

Phase 2/3 study of livmoniplimab in combination with ... A phase 1 study in HCC showed an overall response rate (ORR) of 42% (5/12) when combining livmoniplimab with the programmed cell death 1 ...

6. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO.2024.42.16_suppl.TPS4190

Phase 2/3 study of livmoniplimab in combination with ... Background: Most patients with hepatocellular carcinoma (HCC) present with advanced unresectable or metastatic disease and survival rates remain poor. While ...