Livmoniplimab + Budigalimab for Cancer

Recruiting at 69 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: AbbVie

Must not be taking: Immunosuppressants

Disqualifiers: Immunodeficiency, Transplantation, CNS metastases, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing two experimental drugs, livmoniplimab and budigalimab, to see if they can help patients who need new treatment options by boosting their immune systems. Budigalimab is an experimental drug being tested for its effectiveness.

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.

What data supports the effectiveness of the drug Livmoniplimab + Budigalimab for cancer?

Research shows that budigalimab, a component of the treatment, has been studied in patients with certain types of cancer like non-small cell lung cancer and head and neck cancer, demonstrating safety and some effectiveness. Additionally, similar drugs that target PD-1, like cadonilimab, have been approved for treating other cancers, suggesting potential effectiveness. ^{1 2 3 4 5}

Is the combination of Livmoniplimab and Budigalimab generally safe for humans?

Budigalimab, one of the components of the treatment, has been tested in early clinical trials and showed a safety profile consistent with other similar treatments, with some patients experiencing immune-related side effects. No severe treatment-related deaths were reported, indicating it is generally safe, but monitoring for side effects is important. ^{3 6 7 8 9}

What makes the drug Livmoniplimab + Budigalimab unique for cancer treatment?

Livmoniplimab + Budigalimab is unique because it combines two monoclonal antibodies, one targeting PD-1 (a protein that helps cancer cells evade the immune system) and the other potentially targeting a different immune checkpoint, offering a novel approach to enhance the body's immune response against cancer. ^{2 3 5 8 10}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• ABBV-151 (Monoclonal Antibodies)
• Budigalimab (Monoclonal Antibodies)

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).

Participant Groups

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

Findings from Research

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 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 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]

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 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]

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]

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 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]

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]

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]

References

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

Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC. [2019]

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

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

3. Germany 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. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Cadonilimab: First Approval. [2022]

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

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

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

Linear IgA Disease of the Gingiva Following Nivolumab Therapy. [2020]

7. France 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. [2022]

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

Model Informed Dosing Regimen and Phase I Results of the Anti-PD-1 Antibody Budigalimab (ABBV-181). [2021]

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

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023]

10. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]