Livmoniplimab + Budigalimab for Bladder Cancer

(LIVIGNO-3 Trial)

Not currently recruiting at 49 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AbbVie

Must not be taking: Antibody-drug conjugates

Disqualifiers: Multiple prior chemotherapies, Recent radiation, Transplant history, 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: Unknown

Duration: Up to approximately 3.5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose, safety, and effectiveness of the new drugs livmoniplimab and budigalimab (also known as ABBV-181) for treating bladder cancer that has spread and recurred after initial treatment. Researchers will divide participants into three groups: two groups will receive different doses of the new drug combination, and the third group will receive one of three standard chemotherapy drugs. Individuals with confirmed bladder cancer that has spread and worsened after previous treatments may be suitable for this trial. Participants must visit the hospital regularly for check-ups and tests throughout the study, which could last up to 3.5 years. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 to get a clear answer.

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

Research shows that livmoniplimab and budigalimab have been studied together to find the optimal dose and ensure safety and tolerability. These studies aim to determine the right amount of the drugs that is both effective and safe.

Although exact details on side effects are not available, the progression to more advanced trials suggests that earlier studies found the combination to be generally well-tolerated. Serious side effects were not common enough to halt the research. However, new treatments can still have unexpected side effects.

Participants in these studies typically undergo regular medical check-ups to monitor for any negative effects. This process helps researchers ensure the treatment remains safe as more people use it. It is crucial to consult a healthcare provider to understand the potential risks and benefits 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 bladder cancer because these treatments represent a fresh approach compared to the standard chemotherapy options like cisplatin and methotrexate. Livmoniplimab and Budigalimab are monoclonal antibodies, which means they are designed to target specific proteins involved in cancer cell growth, potentially leading to more precise and effective treatment. This targeted approach could offer better outcomes with fewer side effects than traditional chemotherapy. Additionally, by combining two different antibodies, there’s hope for a synergistic effect, enhancing the body's immune response against cancer cells more effectively than current treatments.

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

Research has shown that livmoniplimab, when combined with budigalimab, yields promising early results. Initial studies found this combination to be well-tolerated, indicating potential safety for patients. Early data also demonstrated positive signs of effectiveness in treating certain cancers. In this trial, participants will receive varying doses of livmoniplimab combined with budigalimab in separate arms. These findings suggest that this combination could offer hope for managing urothelial carcinoma, particularly for those whose cancer has returned or worsened after initial treatments. ^{2 6 7 8 9}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with metastatic urothelial carcinoma who've seen their cancer progress after treatments including checkpoint inhibitors and platinum-based therapies. They must have a measurable lesion, confirmed diagnosis of predominant transitional cell histology, and a life expectancy of at least 3 months.

Inclusion Criteria

My cancer is mainly urothelial carcinoma, confirmed by tests.

My cancer has spread to other parts of my body, confirmed by scans.

My doctor expects me to live at least 3 more months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either livmoniplimab in combination with budigalimab or chemotherapy (docetaxel, paclitaxel, or gemcitabine) based on randomization

Up to approximately 3.5 years

Regular visits at a hospital or clinic for medical assessments, blood tests, questionnaires, and scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Budigalimab
• Livmoniplimab

Trial Overview The trial is testing the safety and effectiveness of two doses of Livmoniplimab combined with Budigalimab versus standard chemotherapy (Docetaxel, Paclitaxel or Gemcitabine). Participants are randomly assigned to one of three groups in equal numbers across multiple global sites.

How Is the Trial Designed?

Group I: Arm 3: Docetaxel, Paclitaxel, or Gemcitabine Experimental Treatment 3 Interventions

Participants will receive docetaxel, paclitaxel, or gemcitabine, investigator's choice, as part of the approximately 3.5 years study duration.

Group II: Arm 2: Livmoniplimab (Dose B) + Budigalimab Experimental Treatment 2 Interventions

Participants will receive livmoniplimab (dose B) in combination with budigalimab, as part of the approximately 3.5 years study duration.

Group III: Arm 1: Livmoniplimab (Dose A) + Budigalimab Experimental Treatment 2 Interventions

Participants will receive livmoniplimab (dose A) in combination with budigalimab, as part of the approximately 3.5 years study duration.

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

In a study of 848 muscle-invasive bladder cancer patients, those who did not respond to PD-L1 blockade therapy were found to have a high angiogenesis signature, indicating a link between this signature and an immunosuppressive tumor environment.

The research identified a specific subgroup of patients resistant to immune checkpoint blockade, characterized by high angiogenesis and low tumor mutation burden, suggesting that combining these factors could help better predict patient responses to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating angiogenesis signature and tumor mutation burden for improved patient stratification in immune checkpoint blockade therapy for muscle-invasive bladder cancer. Shao, F., Jin, K., Li, B., et al.[2023]

Avelumab, an antibody targeting PD-L1, showed significant antitumor effects in a bladder cancer model, indicating its potential as an effective treatment for non-muscle invasive urothelial carcinoma.

The study found that the antitumor effects of avelumab were more reliant on CD4 T cells rather than CD8 T cells, suggesting that enhancing the adaptive immune response could improve treatment outcomes for bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti-PD-L1 Immune Checkpoint Inhibitor. Vandeveer, AJ., Fallon, JK., Tighe, R., et al.[2021]

The study identified inflammatory cancer-associated fibroblasts (iCAFs) in bladder cancer and developed a signature of 278 markers that can predict patient prognosis and response to immunotherapy, based on analysis of two single-cell RNA sequencing datasets and validation in a larger cohort of 519 patients.

A specific subpopulation of iCAFs, termed 'LOXL2+ iCAFs', was found to promote cancer cell proliferation and invasion through the IL32 pathway, suggesting that LOXL2 could be a promising therapeutic target for bladder cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated Analysis Revealed an Inflammatory Cancer-Associated Fibroblast-Based Subtypes with Promising Implications in Predicting the Prognosis and Immunotherapeutic Response of Bladder Cancer Patients. Chen, H., Yang, W., Xue, X., et al.[2022]

The study found that the ratio of IgG1 to IgA in bladder cancer patients serves as a significant prognostic indicator, correlating with better outcomes in anti-PD-L1 immunotherapy, particularly in the IMVigor210 study cohort.

A new predictive tool called PRedIctive MolecUlar Signature (PRIMUS) was developed, which integrates B-cell, natural killer cell, and T-cell signatures to more accurately predict responses to anti-PD-L1 therapy, outperforming traditional methods like PD-L1 expression scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accounting for B-cell Behavior and Sampling Bias Predicts Anti-PD-L1 Response in Bladder Cancer. Dyugay, IA., Lukyanov, DK., Turchaninova, MA., et al.[2023]

The ARHGAP family genes are linked to a tumor-promoting microenvironment in bladder cancer, characterized by immune cell infiltration patterns that may lead to T-cell exhaustion.

Silencing specific ARHGAP genes (ARHGAP5, ARHGAP17, and ARHGAP24) significantly reduced bladder cancer cell proliferation, migration, and metastasis, suggesting these genes play a critical role in cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcriptomic Analysis Identified ARHGAP Family as a Novel Biomarker Associated With Tumor-Promoting Immune Infiltration and Nanomechanical Characteristics in Bladder Cancer. Yang, C., Wu, S., Mou, Z., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03821935

NCT03821935 | Study to Determine the Safety, Tolerability, ... The study will determine the recommended Phase 2 dose (RP2D) of livmoniplimab (ABBV-151) administered as monotherapy and in combination with budigalimab ...

2. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03821935/

Clinical Trial: NCT03821935 The study will determine the recommended Phase 2 dose (RP2D) of ABBV-151 administered as monotherapy and in combination with budigalimab (ABBV-181)

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39534099/

First-in-human phase 1 dose-escalation results with ... Conclusion: Livmoniplimab was well-tolerated as monotherapy and in combination with budigalimab in the dose-escalation phase. Encouraging preliminary efficacy ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06632951?cond=Transitional%20cell%20carcinoma%20OR%20%22carcinoma%20of%20transitional%20epithelial%20cell%22%20OR%20%22%20carcinoma%20of%20urothelial%20cell%22%20OR%20%22%20carcinoma,%20urothelial,%20malignant%22%20OR%20%22%20transitional%20carcinoma%22%20OR%20%22%20transitional%20epithelial%20cell%20carcinoma%22%20OR%20%22%20urothelial%20cell%20carcinoma%22&aggFilters=status:not%20rec&viewType=Table&rank=3

NCT06632951 | Study to Evaluate Adverse Events and ... The purpose of this study is to evaluate the optimized dose, adverse events, and efficacy of livmoniplimab in combination with budigalimab. Livmoniplimab is an ...

5. trial.medpath.com trial.medpath.com/clinical-trial/cda472513334bcb6/livmoniplimab-abbv-151-budigalimab-abbv-181-solid-tumors

Study to Determine the Safety, Tolerability, Pharmacokinetics ... The study will determine the recommended Phase 2 dose (RP2D) of livmoniplimab (ABBV-151) administered as monotherapy and in combination with budigalimab ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03821935

NCT03821935 | Study to Determine the Safety, Tolerability, ... The study will determine the recommended Phase 2 dose (RP2D) of livmoniplimab (ABBV-151) administered as monotherapy and in combination with budigalimab ...

7. bcan.org bcan.org/clinicaltrials/study-to-determine-the-safety-tolerability-pharmacokinetics-and-rp2d-of-abbv-151-as-a-single-agent-and-in-combination-with-abbv-181-in-participants-with-locally-advanced-or-metastatic-solid-tumors/

Study to Determine the Safety, Tolerability ... The study will determine the recommended Phase 2 dose (RP2D) of livmoniplimab (ABBV-151) administered as monotherapy and in combination with budigalimab (ABBV- ...

8. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=M19-345

M19-345 The study will determine the recommended Phase 2 dose (RP2D) of livmoniplimab (ABBV-151) administered as monotherapy and in combination with budigalimab (ABBV- ...

9. data.niaid.nih.gov data.niaid.nih.gov/resources?id=2295725

Study to Determine the Safety, Tolerability, ... The study will determine the recommended Phase 2 dose (RP2D) of livmoniplimab (ABBV-151) administered as monotherapy and in combination with budigalimab ...