Livmoniplimab + Budigalimab for Bladder Cancer

(LIVIGNO-3 Trial)

Recruiting at 29 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

150 Participants Needed

Trial Summary

What is the purpose of this trial?

Urothelial carcinoma (UC) is the ninth most common cancer type worldwide. While the treatment of front-line metastatic urothelial carcinoma (mUC) has improved, there remains a high unmet need for effective therapies for participants who have recurrent disease and disease that has progressed after frontline treatment. The purpose of this study is to evaluate the optimized dose, adverse events, and efficacy of livmoniplimab in combination with budigalimab. Livmoniplimab is an investigational drug being developed for the treatment of mUC. There are 3 treatment arms in this study and participants will be randomized in a 1:1:1 ratio. Participants will either receive livmoniplimab (at one of 2 different doses) in combination with budigalimab (another investigational drug), or either docetaxel, paclitaxel, or gemcitabine (based on investigator's choice). Approximately 150 adult participants will be enrolled in the study across 56 sites worldwide. In arm 1, participants will receive intravenously (IV) infused livmoniplimab (dose A) in combination with IV infused budigalimab. In arm 2, participants will receive IV infused livmoniplimab (dose B) in combination with IV infused budigalimab. In arm 3 (control), participants will receive the investigator's choice: IV infused or injected docetaxel; IV infused or injected paclitaxel; or IV infused gemcitabine. The estimated duration of the study is up to approximately 3.5 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, questionnaires, and scans.

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.

How is the drug Livmoniplimab + Budigalimab unique for bladder cancer treatment?

Livmoniplimab and Budigalimab are unique because they target specific immune pathways, potentially offering a novel approach compared to traditional treatments like BCG or PD-L1 inhibitors. This combination may work by modulating the immune system differently, which could be beneficial for patients who do not respond to existing therapies. ^{1 2 3 4 5}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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.

I have at least one tumor that can be measured.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. Switzerland 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. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Accounting for B-cell Behavior and Sampling Bias Predicts Anti-PD-L1 Response in Bladder Cancer. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti-PD-L1 Immune Checkpoint Inhibitor. [2021]

4. United States 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. [2023]

5. Switzerland 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. [2022]