Livmoniplimab + Budigalimab + Chemotherapy for Lung Cancer

(LIVIGNO-4 Trial)

Recruiting at 75 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: AbbVie

Disqualifiers: Prior systemic therapy for NSCLC

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: 16 weeks

840 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for individuals with metastatic non-squamous non-small cell lung cancer (NSCLC), a challenging type of lung cancer that has spread. The trial aims to determine the optimal dose and evaluate the effectiveness and side effects of a new drug combination involving livmoniplimab and budigalimab (both experimental drugs) plus chemotherapy, compared to a known treatment with pembrolizumab and chemotherapy. Suitable candidates for this trial have NSCLC that has spread, have not received prior treatment for it, and do not have certain specific genetic mutations. Participants will receive different treatments in two stages to identify the most effective approach. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in lung 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 the combination of livmoniplimab and budigalimab has a manageable safety profile for patients with advanced solid tumors. While some side effects may occur, they are usually mild and expected. In earlier studies, this combination was well tolerated and significantly improved outcomes for patients with various solid tumors, including liver cancer.

For budigalimab alone, studies in patients with different cancers, such as lung cancer, have demonstrated its safety. Patients generally did not experience any unexpected or severe safety issues with budigalimab.

It is important to note that livmoniplimab and budigalimab remain experimental drugs. Ongoing research is carefully monitoring their safety to ensure they are suitable for wider use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because they introduce innovative approaches that could enhance effectiveness. Livmoniplimab and Budigalimab are novel immunotherapy agents that work by boosting the immune system's ability to target and destroy cancer cells. Unlike traditional chemotherapy, which directly targets and kills cancer cells, these drugs aim to empower the body's natural defenses. Moreover, the combination of these immunotherapies with chemotherapy, including Pemetrexed, may improve treatment outcomes by tackling the cancer from multiple angles. This multi-faceted approach has the potential to offer better control over tumor growth and possibly extend survival rates for patients.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that combining livmoniplimab and budigalimab holds promise for treating solid tumors, such as lung cancer. One study reported a 42% success rate in shrinking certain cancer types with this combination, indicating potential effectiveness. In this trial, some participants will receive both livmoniplimab and budigalimab. Budigalimab alone, which other participants may receive, demonstrated a 12.4% success rate in treating non-small cell lung cancer (NSCLC) in earlier studies. These findings suggest that using livmoniplimab and budigalimab together might offer new hope for treating advanced non-squamous NSCLC. ^{1 2 3 4 6}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with untreated metastatic non-squamous NSCLC, who have at least one measurable lesion and no EGFR or ALK mutations. Participants should not have other genomic abnormalities treatable by approved therapies, must expect to live at least 3 more months, and need proper organ function.

Inclusion Criteria

My lung cancer is advanced, not squamous, and lacks certain genetic mutations.

My doctor expects me to live at least 3 more months and my organs are working well.

I have a tumor that can be measured by scans.

Exclusion Criteria

I have received treatment for my advanced lung cancer.

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 plus chemotherapy or pembrolizumab plus chemotherapy for 4 cycles

16 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 55 months

Extension

Participants may continue to receive treatment with livmoniplimab and budigalimab plus pemetrexed or pembrolizumab plus pemetrexed

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Budigalimab
• Livmoniplimab
• Pemetrexed

Trial Overview The trial is testing Livmoniplimab combined with Budigalimab plus chemotherapy against Pembrolizumab with chemotherapy in two stages. Stage 1 has four groups receiving various treatments; Stage 2 has two groups based on the optimized dose from Stage 1.

How Is the Trial Designed?

Group I: Stage 2 (Arm 2): Placebo Experimental Treatment 4 Interventions

Participants will receive placebo + pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed.

Group II: Stage 2 (Arm 1): Livmoniplimab (Dose Optimized) Experimental Treatment 5 Interventions

Participants will receive livmoniplimab (dose optimized) + budigalimab + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.

Group III: Stage 1 (Cohort 4): Pembrolizumab Experimental Treatment 4 Interventions

Participants will receive pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed.

Group IV: Stage 1 (Cohort 3): Budigalimab Experimental Treatment 4 Interventions

Participants will receive budigalimab + chemotherapy for 4 cycles followed by budigalimab + pemetrexed.

Group V: Stage 1 (Cohort 2): Livmoniplimab Dose B Experimental Treatment 5 Interventions

Participants will receive livmoniplimab (dose B) + budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.

Group VI: Stage 1 (Cohort 1): Livmoniplimab Dose A Experimental Treatment 5 Interventions

Participants will receive livmoniplimab (dose A)+ budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.

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 pooled analysis of 444 patients with PD-L1-negative advanced/metastatic non-small cell lung cancer (NSCLC), pembrolizumab combined with chemotherapy significantly improved overall survival (hazard ratio 0.63) and progression-free survival (hazard ratio 0.68) compared to chemotherapy alone.

Despite high rates of adverse events (99.2% in the pembrolizumab group), the combination therapy was manageable and resulted in an impressive objective response rate of 87.5% and a 3-year overall survival rate of 100% for patients completing 2 years of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer without tumor PD-L1 expression: A pooled analysis of 3 randomized controlled trials. Borghaei, H., Langer, CJ., Paz-Ares, L., et al.[2021]

Atezolizumab, cemiplimab, and pembrolizumab are established as standard first-line immunotherapy options for patients with advanced non-small cell lung cancer (NSCLC) who have high PD-L1 expression (≥50%).

The consensus among 25 Spanish lung cancer experts indicates that these therapies can be tailored to specific patient subgroups, enhancing treatment decision-making based on differences observed in pivotal clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement. Isla, D., Sánchez, A., Casal, J., et al.[2023]

In a phase 3 trial involving 308 patients with advanced non-small-cell lung cancer (NSCLC) and EGFR exon 20 insertions, the combination of amivantamab and chemotherapy significantly improved progression-free survival compared to chemotherapy alone, with a median of 11.4 months versus 6.7 months.

The combination therapy also showed a higher response rate, with 73% of patients achieving a complete or partial response compared to 47% in the chemotherapy-only group, indicating that amivantamab enhances the effectiveness of standard chemotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. Zhou, C., Tang, KJ., Cho, BC., et al.[2023]

In a phase III trial involving 657 patients with advanced EGFR-mutated non-small-cell lung cancer, both amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy significantly improved progression-free survival (PFS) compared to standard chemotherapy, with median PFS of 6.3 and 8.3 months versus 4.2 months, respectively.

The combination therapies also showed a higher objective response rate (64% and 63% for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively) compared to chemotherapy (36%), although the amivantamab-lazertinib-chemotherapy regimen had more hematologic adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Passaro, A., Wang, J., Wang, Y., et al.[2023]

The study confirmed that the Ventana BenchMark XT platform can reliably detect PD-L1 levels in non-small cell lung cancer (NSCLC) using the 22C3 antibody, showing a high correlation with results from the Dako platform (Pearson's correlation score of 0.91).

Using the Ventana platform, 87.8% of cases showed consistent PD-L1 scoring with Dako, indicating that it can effectively stratify patients for pembrolizumab immunotherapy, ensuring accurate treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Harmonization Study for the Use of 22C3 PD-L1 Immunohistochemical Staining on Ventana's Platform. Neuman, T., London, M., Kania-Almog, J., et al.[2018]

Pembrolizumab, when combined with carboplatin and pemetrexed, significantly improves overall and progression-free survival rates in patients with non-small cell lung cancer (NSCLC), demonstrating its efficacy as a treatment option.

This case report highlights a unique instance of immune-mediated sarcoidosis developing in a patient with NSCLC after receiving pembrolizumab, indicating potential immune-related side effects of this therapy that require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. Fakhri, G., Akel, R., Salem, Z., et al.[2022]

In a phase Ib trial involving 26 patients with advanced non-small-cell lung cancer, the combination of bavituximab with pemetrexed and carboplatin was found to be well tolerated, with no dose-limiting toxicities reported.

The treatment showed a preliminary overall response rate of 28%, with median progression-free survival of 4.8 months and overall survival of 12.2 months, suggesting that while bavituximab is safe, its efficacy needs further enhancement compared to standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Bavituximab With Carboplatin and Pemetrexed in Chemotherapy-Naive Advanced Nonsquamous Non-Small-Cell Lung Cancer. Grilley-Olson, JE., Weiss, J., Ivanova, A., et al.[2019]

In a phase I study involving 113 patients with advanced solid tumors, MK-4166 was found to be tolerable, with only 8% of patients experiencing treatment-related grade ≥3 adverse events and no treatment-related deaths reported.

The combination of MK-4166 with pembrolizumab showed promising efficacy, particularly in patients with immune checkpoint inhibitor (ICI)-naïve melanoma, achieving an objective response rate of 62%, indicating potential for effective treatment in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of MK-4166, an Anti-human Glucocorticoid-Induced TNF Receptor Antibody, Alone or with Pembrolizumab in Advanced Solid Tumors. Papadopoulos, KP., Autio, K., Golan, T., et al.[2022]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., 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]

A 73-year-old man with advanced non-small cell lung cancer experienced gingival linear immunoglobulin A disease after one year of treatment with the immune checkpoint inhibitor nivolumab, highlighting a rare adverse effect of this therapy.

The condition was effectively managed with systemic steroids, emphasizing the importance of monitoring for immune-related adverse events during and after immunotherapy treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linear IgA Disease of the Gingiva Following Nivolumab Therapy. Jonna, S., Neiders, M., Lakshmanan, S., et al.[2020]

Citations

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First-in-human phase 1 study of budigalimab, an anti-PD-1 ... 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.

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Safety, pharmacokinetics, and efficacy of budigalimab with ... Results showed an overall response rate (ORR) of 12.4% and median overall survival of 5.6 months [17]. Preclinical data suggest cytotoxic agents may induce ...

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NCT03000257 | A Study of Budigalimab (ABBV-181) in ... Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. Cancer Treat Res Commun. 2021;28 ...

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Safety and efficacy of the PD-1 inhibitor ABBV-181 in ... Results: As of January 15, 2018, 53 pts were treated with ABBV-181: 25 in dose finding, 17, 6, and 5 in multi-histology, HNSCC and NSCLC cohorts, respectively.

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M19-037 A study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-927 with ABBV-368, Budigalimab (ABBV-181) and/or ...