Livmoniplimab + Budigalimab for Cancer

Not currently recruiting at 94 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

Must not be taking: Immunosuppressants

Disqualifiers: Immunodeficiency, Transplantation, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the optimal dose for two experimental cancer treatments, livmoniplimab (ABBV-151) and budigalimab (ABBV-181), both individually and in combination. The researchers aim to assess the safety and effectiveness of these treatments for various cancers, including ovarian, pancreatic, bladder, and lung cancer. This trial targets individuals with specific cancer types that have not responded to other treatments or who cannot undergo standard treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive these new treatments.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot have received any anticancer therapy, including chemotherapy or immunotherapy, within a certain period before starting the study drug. Also, you should not use immunosuppressive medication within 14 days before the first dose.

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

Research shows that livmoniplimab and budigalimab are generally safe. In earlier studies, patients tolerated livmoniplimab well, both alone and in combination with budigalimab. One study found that using both drugs together did not cause severe side effects, even at different doses, indicating the treatment's general safety.

Similarly, patients with various solid tumors tolerated budigalimab alone well. Early results from these studies did not show high rates of severe side effects, suggesting it is likely safe.

These findings come from early research stages. Researchers use these studies to determine safe dose levels for future trials, helping ensure treatments remain as safe as possible when tested in larger groups. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Livmoniplimab and Budigalimab because, unlike traditional treatments for cancer that often involve chemotherapy or radiation, these drugs target the immune system. Livmoniplimab is designed to enhance the body's natural immune response against tumors, while Budigalimab is an antibody that helps unleash this response by inhibiting specific checkpoints that cancer cells use to hide from the immune system. This immune-based approach could lead to more effective and potentially less toxic treatment options for various cancers like ovarian granulosa cell tumors, urothelial cancer, and pancreatic adenocarcinoma. By harnessing the power of the immune system, these treatments hold promise for improved outcomes and a new way of tackling cancer.

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

Research has shown that combining livmoniplimab and budigalimab yields promising results in treating certain cancers. In this trial, participants will receive various combinations of these drugs across different treatment arms. A study with liver cancer patients showed that nearly half experienced tumor shrinkage. Livmoniplimab is generally safe when used alone or with budigalimab. Budigalimab has also proven effective against several cancers, including lung cancer. These early findings suggest that this combination might be effective for other types of cancer as well. ^{1 2 3 4 6}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors, including specific cancers of the bladder, urinary tract, pancreas, liver, and head/neck. Participants must have tried some treatments like platinum-based regimens or PD1/PDL1 antagonists without success. They should be in good physical condition (ECOG 0-1) and have proper organ function.

Inclusion Criteria

My pancreatic cancer worsened after at least one treatment.

I have advanced NSCLC and have had one chemotherapy and one anti-PD-(L)1 treatment.

My blood, kidney, liver, and clotting tests are normal.

Exclusion Criteria

I haven't had any cancer treatment in the last 28 days or within 5 half-lives of the treatment, whichever is shorter.

I have had a primary immunodeficiency, bone marrow or organ transplant, or tuberculosis.

I have been treated with immunotherapies before, except if I have urothelial cancer or head and neck cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Various doses of Livmoniplimab and Budigalimab are administered to determine the Recommended Phase 2 Dose (RP2D)

Up to 28 days

Dose Expansion

Participants receive Livmoniplimab and Budigalimab at the RP2D to assess safety, tolerability, and preliminary efficacy

Up to 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 9 months

What Are the Treatments Tested in This Trial?

Interventions

• ABBV-151
• Budigalimab

Trial Overview

The study tests Livmoniplimab alone and combined with Budigalimab to find a safe dose level and check their effects on cancer. It has two parts: first finding the right doses (dose escalation), then giving those doses to more people to learn more about safety and effectiveness (dose expansion).

How Is the Trial Designed?

Group I: Dose Expansion: Cohort 8 Livmoniplimab + Budigalimab Experimental Treatment 2 Interventions

Participants with non-small cell lung cancer (NSCLC) \[programmed death ligand 1 (PDL1) relapsed/refractory (R/R)\] will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.

Group II: Dose Expansion: Cohort 7 Livmoniplimab + Budigalimab Experimental Treatment 2 Interventions

Participants with PD-1-naïve microsatellite stable colorectal cancer (MSS-CRC) \[unselected\] will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.

Group III: Dose Expansion: Cohort 6 Livmoniplimab + Budigalimab Experimental Treatment 2 Interventions

Participants with PD-1-ref head and neck squamous cell carcinoma (HNSCC) will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.

Group IV: Dose Expansion: Cohort 5 Livmoniplimab + Budigalimab Experimental Treatment 2 Interventions

Participants with PD-1-naïve hepatocellular carcinoma (HCC) will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.

Group V: Dose Expansion: Cohort 4 Livmoniplimab + Budigalimab Experimental Treatment 2 Interventions

Participants with PD-1-ref urothelial cancer will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.

Group VI: Dose Expansion: Cohort 3 Livmoniplimab + Budigalimab Experimental Treatment 2 Interventions

Participants with programmed cell death protein 1 (PD-1)-naïve pancreatic adenocarcinoma will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.

Group VII: Dose Expansion: Cohort 12B Livmoniplimab + Budigalimab Experimental Treatment 2 Interventions

Participants with PD-1-naïve ovarian granulosa (OG) cell tumors will receive livmoniplimab at the Dose C Q3W plus budigalimab Dose B administered Q3W.

Group VIII: Dose Expansion: Cohort 12A Livmoniplimab + Budigalimab Experimental Treatment 2 Interventions

Participants with PD-1-naïve ovarian granulosa (OG) cell tumors will receive livmoniplimab at the Dose B Q3W plus budigalimab Dose B administered Q3W.

Group IX: Dose Expansion: Cohort 11C Budigalimab Experimental Treatment 1 Intervention

Participants with PD-1-ref urothelial cancer will receive budigalimab Dose B administered Q3W.

Group X: Dose Expansion: Cohort 11B Livmoniplimab + Budigalimab Experimental Treatment 2 Interventions

Participants with PD-1-ref urothelial cancer will receive livmoniplimab at the Dose C Q3W plus budigalimab Dose B administered Q3W.

Group XI: Dose Expansion: Cohort 11A Livmoniplimab + Budigalimab Experimental Treatment 2 Interventions

Participants with PD-1-ref urothelial cancer will receive livmoniplimab at the Dose B Q3W plus budigalimab Dose B administered Q3W.

Group XII: Dose Expansion: Cohort 10B Livmoniplimab + Budigalimab Experimental Treatment 2 Interventions

Participants with MSS-CRC (CMS4 enriched) will receive livmoniplimab at the dose C Q3W plus budigalimab Dose B administered Q3W.

Group XIII: Dose Expansion: Cohort 10A Livmoniplimab + Budigalimab Experimental Treatment 2 Interventions

Participants with microsatellite stable colorectal cancer (MSS-CRC) \[consensus molecular subtype 4 (CMS4) enriched\] will receive livmoniplimab at the dose B Q3W plus budigalimab Dose B administered Q3W.

Group XIV: Dose Escalation: Cohort 2 Livmoniplimab + Budigalimab Experimental Treatment 2 Interventions

Various doses of Livmoniplimab + Budigalimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D).

Group XV: Dose Escalation: Cohort 1 Livmoniplimab Experimental Treatment 1 Intervention

Various doses of Livmoniplimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D).

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

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

Cadonilimab is a bi-specific antibody targeting PD-1 and CTLA-4, developed for treating various solid tumors, and was approved in China in June 2022 specifically for patients with relapsed or metastatic cervical cancer who have not responded to platinum-based chemotherapy.

The approval of cadonilimab marks a significant milestone in cancer treatment, providing a new therapeutic option for patients with advanced cervical cancer after standard chemotherapy has failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cadonilimab: First Approval. Keam, SJ.[2022]

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

Budigalimab, a monoclonal antibody targeting the PD-1 receptor, demonstrated a manageable safety profile in a phase I trial with 59 patients, showing only 18.6% experiencing immune-related adverse events, and no grade 5 adverse events reported.

The drug achieved over 99% PD-1 receptor saturation within 2 hours of dosing, indicating effective pharmacodynamics, and showed comparable pharmacokinetics and safety profiles between Japanese and Western patients, supporting its potential as a viable treatment for advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Model Informed Dosing Regimen and Phase I Results of the Anti-PD-1 Antibody Budigalimab (ABBV-181). Powderly, J., Spira, A., Kondo, S., et al.[2021]

The combination of nivolumab and erlotinib was found to be tolerable in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC), with treatment-related grade 3 toxicities occurring in only five out of twenty patients, and no severe grade 4 toxicities reported.

Among the TKI-treated patients, the objective response rate was 15%, with some patients experiencing durable responses lasting up to 38.2 months, indicating potential efficacy of this combination therapy in managing advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC. Gettinger, S., Hellmann, MD., Chow, LQM., et al.[2019]

The immune checkpoint inhibitor COM701, which targets the PVRIG protein, has demonstrated early signs of effectiveness in treating advanced solid tumors in an ongoing phase I trial.

COM701 shows potential for enhanced efficacy when used in combination with nivolumab, suggesting a promising approach for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COM701 Shows Antitumor Activity, +/- Nivolumab. [2021]

In a systematic review of 18 phase III clinical trials involving 12,172 lung cancer patients, the use of PD-(L)1 immune-checkpoint inhibitors (ICIs) did not show a significant increase in rheumatic immune-related adverse events (irAEs) compared to controls, suggesting these events may be underreported in clinical settings.

However, patients receiving ICIs experienced significantly higher rates of severe back pain and, when combined with chemotherapy, a notable increase in arthralgia, indicating that while overall rheumatic irAEs are low, specific types of pain are associated with ICI treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rheumatic immune-and nonimmune-related adverse events in phase 3 clinical trials assessing PD-(L)1 checkpoint inhibitors for lung cancer: A systematic review and meta-analysis. Veccia, A., Kostine, M., Tison, A., et al.[2022]

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]

A retrospective analysis of adverse events related to PD-1/PD-L1 inhibitors revealed a significant association between Pembrolizumab and hepatitis B reactivation (HBVr), with a reporting odds ratio of 2.32, indicating a higher risk compared to other treatments.

No cases of HBVr were reported with Ipilimumab or Avelumab, suggesting that not all immune checkpoint inhibitors carry the same risk, highlighting the need for further prospective studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. Burns, EA., Muhsen, IN., Anand, K., et al.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8783908/

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

We present the safety, efficacy, pharmacokinetic (PK), and pharmacodynamic data from patients enrolled in the head and neck squamous cell carcinoma (HNSCC) and ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03000257

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 ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2468294221001039

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 ...

4.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(19)48904-7/fulltext

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.

5.

ascpt.onlinelibrary.wiley.com

ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.12855

Model Informed Dosing Regimen and Phase I Results of the ...

Budigalimab demonstrated evidence of antitumor activity in tumor types (renal cell carcinoma, non-small cell lung cancer, and squamous cell ...

6.

abbvieclinicaltrials.com

abbvieclinicaltrials.com/study/?id=M19-037

M19-037

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