ABBV-514 + Budigalimab for Lung & Head and Neck Cancers

Recruiting at 63 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

Disqualifiers: EGFR mutations, ALK rearrangements, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

512 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for certain advanced cancers, including lung and head and neck cancers, to assess their safety and how the body processes them. Participants receive a drug called Azirkitug, either alone or with other drugs, to determine the best dose and identify side effects. Individuals with advanced non-small cell lung cancer or head and neck cancer that has worsened despite standard treatments might be suitable for this trial. Participants must attend regular medical appointments to monitor treatment effects. As a Phase 1 trial, participants will be among the first to receive Azirkitug, aiding researchers in understanding how this new treatment works in people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves investigational drugs, it's best to discuss your current medications with the study doctors to ensure there are no interactions.

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

Research has shown that Azirkitug (ABBV-514), whether used alone or with Budigalimab or Bevacizumab, undergoes careful safety monitoring in clinical trials. Early studies have assessed its safety both as a standalone treatment and in combination with Budigalimab, checking for side effects. Initial results suggest the treatment is generally well-tolerated, though individual experiences may vary.

For the combination of Azirkitug with Budigalimab, past studies demonstrated some safety and effectiveness in treating head and neck and lung cancers. Bevacizumab, already FDA-approved for other uses, provides some confidence in its safety. However, its safety with Azirkitug remains under study to ensure suitability for specific cancers.

As this trial is in its early stages, it focuses on determining the right doses and understanding the treatment's safety for participants. This trial is a crucial step to ensure the treatment's safety before proceeding further. Participants are monitored for side effects, and the medical team will adjust as needed to maintain safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ABBV-514 because it represents a new approach in targeting cancer cells. Unlike many standard treatments for lung and head and neck cancers, which often focus on traditional chemotherapy or radiation, ABBV-514 is an antibody-drug conjugate that specifically targets and delivers a toxic payload directly to cancer cells, potentially reducing harm to healthy cells. Additionally, combining ABBV-514 with Budigalimab, an innovative immunotherapy that enhances the body's own immune response against cancer, offers a promising dual approach. This combination could lead to more effective and targeted treatment strategies, providing hope for improved outcomes in these challenging cancer types.

What evidence suggests that this trial's treatments could be effective for lung and head and neck cancers?

Research shows that Azirkitug (ABBV-514) is under study as a treatment for Non-Small Cell Lung Cancer (NSCLC) and Head and Neck Squamous Cell Carcinoma (HNSCC). In this trial, participants may receive Azirkitug (ABBV-514) alone or with Budigalimab. Early results from the study examine the safety and efficacy of these treatments. Budigalimab is notable for its design to enhance the immune system's ability to attack cancer cells. Although more data is needed, these treatments show promise by specifically targeting cancer in these conditions. ^{2 4 6 7 8}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with advanced or metastatic NSCLC or HNSCC that have relapsed after platinum-based chemotherapy and PD-1/PD-L1 therapy can join. They must have measurable disease, meet certain lab criteria, and be in good physical condition (ECOG ≤ 1). Those with specific genetic mutations (EGFR, ALK) in NSCLC are excluded.

Inclusion Criteria

Relapsed Non-Small Cell Lung Cancer (NSCLC) Head and Neck Squamous Cell Carcinoma (HNSCC) dose-expansion cohorts only: Must have histologically or cytologically confirmed advanced or metastatic NSCLC or HNSCC that is not suitable for surgical resection and/or radiation therapy and has been treated with platinum-based chemotherapy and a programmed cell death (PD)-1 or PD ligand 1 (PD-L1) targeting agent (separately or in combination therapy). Must have failed (or refused) treatment with available therapies known to be active for treatment of their disease. Participants enrolled in dose escalation must have disease that is evaluable or measurable per Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Participants enrolled in dose expansion must have measurable disease per RECIST, version 1.1. Eastern Cooperative Oncology Group (ECOG) performance status of <= 1. Laboratory values meeting the criteria outlined in the protocol.

My advanced cancer has not responded to or I cannot tolerate any known treatments.

Exclusion Criteria

My lung cancer has returned but does not have EGFR mutations or ALK rearrangements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ABBV-514 as a monotherapy or in combination with Budigalimab as an Intravenous (IV) Infusion

Up to 2 years

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ABBV-514
• Budigalimab
• Pembrolizumab

Trial Overview The trial is testing ABBV-514 alone or combined with Budigalimab on patients with NSCLC and HNSCC. It aims to find the highest dose patients can tolerate without severe side effects. Participants will receive IV infusions of these drugs for up to two years at hospitals or clinics worldwide.

How Is the Trial Designed?

Group I: Part 9 Dose Expansion: Azirkitug (ABBV-514) + Budigalimab Experimental Treatment 2 Interventions

Participants will receive Azirkitug (ABBV-514) at recommended dose determined in Dose Escalation portion in combination with budigalimab.

Group II: Part 8 Dose Expansion: Azirkitug (ABBV-514) + Bevacizumab Experimental Treatment 2 Interventions

Participants will receive Azirkitug (ABBV-514) at recommended dose determined in Dose Escalation portion in combination with bevacizumab.

Group III: Part 8 Dose Escalation: Azirkitug (ABBV-514) + Bevacizumab Experimental Treatment 2 Interventions

Participants will receive Azirkitug (ABBV-514) in combination with bevacizumab.

Group IV: Part 7 Dose Expansion: Azirkitug (ABBV-514) + Budigalimab Experimental Treatment 2 Interventions

Participants will receive Azirkitug (ABBV-514) at recommended dose determined in Dose Escalation portion in combination with budigalimab.

Group V: Part 6 Dose Expansion: Azirkitug (ABBV-514) + Budigalimab Experimental Treatment 2 Interventions

Participants will receive Azirkitug (ABBV-514) at recommended dose determined in Dose Escalation portion in combination with budigalimab.

Group VI: Part 5 Dose Expansion: Azirkitug (ABBV-514) + Budigalimab Experimental Treatment 2 Interventions

Participants will receive Azirkitug (ABBV-514) at recommended dose determined in Dose Escalation portion in combination with budigalimab.

Group VII: Part 5 Dose Expansion: Azirkitug (ABBV-514) Experimental Treatment 1 Intervention

Participants will receive Azirkitug (ABBV-514) at recommended dose determined in Dose Escalation portion.

Group VIII: Part 4 Dose Expansion: Azirkitug (ABBV-514) + Budigalimab Experimental Treatment 2 Interventions

Participants will receive Azirkitug (ABBV-514) at recommended dose determined in Dose Escalation portion in combination with budigalimab.

Group IX: Part 4 Dose Expansion: Azirkitug (ABBV-514) Experimental Treatment 1 Intervention

Participants will receive Azirkitug (ABBV-514) at recommended dose determined in Dose Escalation portion.

Group X: Part 3 Dose Expansion: Azirkitug (ABBV-514) + Budigalimab Experimental Treatment 2 Interventions

Participants will receive Azirkitug (ABBV-514) at recommended dose determined in Dose Escalation portion in combination with budigalimab.

Group XI: Part 2 Dose Expansion: Azirkitug (ABBV-514) + Budigalimab Experimental Treatment 2 Interventions

Participants will receive Azirkitug (ABBV-514) at recommended dose determined in Dose Escalation portion in combination with budigalimab.

Group XII: Part 2 Dose Expansion: Azirkitug (ABBV-514) Experimental Treatment 1 Intervention

Participants will receive Azirkitug (ABBV-514) at recommended dose determined in Dose Escalation portion.

Group XIII: Part 1 Dose Escalation: Azirkitug (ABBV-514) + Budigalimab Experimental Treatment 2 Interventions

Participants will receive Azirkitug (ABBV-514) in combination with budigalimab.

Group XIV: Part 1 Dose Escalation: Azirkitug (ABBV-514) Experimental Treatment 1 Intervention

Participants will receive Azirkitug (ABBV-514).

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

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

In a study of 34 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with PD-1 inhibitors, 29% experienced hyperprogression, where tumor growth accelerated during treatment.

Hyperprogression was significantly associated with regional recurrence, leading to shorter progression-free survival, but did not affect overall survival, highlighting the need for further research into the mechanisms behind this phenomenon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Saâda-Bouzid, E., Defaucheux, C., Karabajakian, A., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

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]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

A cost-effectiveness analysis of nivolumab versus pembrolizumab in treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) found that nivolumab has a 56% probability of being cost-effective at a willingness-to-pay (WTP) threshold of $100,000 per quality-adjusted life-year (QALY) when dosed at 3 mg/kg biweekly for patients under 72 kg.

For patients over this weight, pembrolizumab is generally the more cost-effective option, especially at higher WTP thresholds, indicating that patient body weight and dosing strategy are crucial factors in treatment decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab vs Pembrolizumab for Treatment of US Patients With Platinum-Refractory Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Network Meta-analysis and Cost-effectiveness Analysis. Pei, R., Shi, Y., Lv, S., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05005403?term=AREA%5BNCTIdSearch%5D(NCT05005403)&rank=1

NCT05005403 | Study to Assess Adverse Events and ... Bevacizumab is an approved product, while Budigalimab and Azirkitug (ABBV-514) are investigational drugs being developed for the treatment of NSCLC, HNSCC, and ...

2. withpower.com withpower.com/trial/phase-1-lung-neoplasms-8-2021-e4040

ABBV-514 + Budigalimab for Lung & Head and Neck ... In a study of 34 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with PD-1 inhibitors, 29% experienced hyperprogression, ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03810-3/fulltext

1076TiP First-in-human study of ABBV-514 as ... This first-in-human trial evaluates safety, pharmacokinetics (PK), and preliminary efficacy of ABBV-514 as monotherapy and in combination with budigalimab (BDG) ...

4. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=M21-410

M21-410 Study to assess adverse events and pharmacokinetics in adult participants with non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-01100

Study to Assess Adverse Events and Pharmacokinetics in ... The purpose of this study is to assess adverse events and pharmacokinetics of Azirkitug (ABBV-514) as a monotherapy and in combination with Budigalimab or ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05005403?intr=ABBV-514&rank=1

Study to Assess Adverse Events and Pharmacokinetics in ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the ...

7. trialx.com trialx.com/clinical-trials/listings/223627/study-to-assess-adverse-events-and-pharmacokinetics-in-adult-participants-with-non-small-cell-lung-cancer-nsclc-head-and-neck-squamous-cell-carcinoma-hnscc-and-other-solid-tumors-receiving-intravenous-iv-infusion-of-azirkitug-abbv-514-alone-or-in-combinat/

Study to Assess Adverse Events and Pharmacokinetics in ... Study to Assess Adverse Events and Pharmacokinetics in Adult Participants With Non-Small Cell Lung Cancer (NSCLC), Head and Neck Squamous ...

8. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT05005403/

Clinical Trial: NCT05005403 The purpose of this study is to assess adverse events and pharmacokinetics of ABBV-514 as a monotherapy and in combination with Pembrolizumab or Budigalimab.