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

Recruiting in Palo Alto (17 mi)

+46 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: AbbVie

Disqualifiers: EGFR mutations, ALK rearrangements, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing two experimental drugs, ABBV-514 and Budigalimab, on adults with specific types of cancer. The goal is to find out if these drugs can help treat lung and head/neck cancers by monitoring their effects and side effects.

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.

What data supports the effectiveness of the drug ABBV-514 + Budigalimab for lung and head and neck cancers?

Budigalimab, a part of the treatment, has shown safety and some effectiveness in early studies for head and neck and lung cancers. Pembrolizumab, another drug in the treatment, is already approved for similar cancers and has shown clinical activity in various solid tumors. ^{1 2 3 4 5}

What safety data exists for Pembrolizumab (Keytruda) in humans?

Pembrolizumab (Keytruda) has been associated with some side effects, including pneumonitis (lung inflammation) occurring in 1%-5% of patients, and other immune-related reactions like hypothyroidism (underactive thyroid) and hyperthyroidism (overactive thyroid). These side effects were observed in clinical trials for various cancers, indicating that while pembrolizumab can be effective, it may also cause significant immune-related side effects. ^{3 5 6 7 8}

What makes the drug combination of ABBV-514, Budigalimab, and Pembrolizumab unique for treating lung and head and neck cancers?

This drug combination is unique because it includes Budigalimab, a new anti-PD-1 inhibitor, which is being studied for its safety and effectiveness in lung and head and neck cancers, potentially offering a novel approach to enhance the immune system's ability to fight these cancers. ^{1 2 3 4 8}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• ABBV-514 (Other)
• Budigalimab (Monoclonal Antibodies)
• Pembrolizumab (Monoclonal Antibodies)

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.

Participant Groups

Group I: Part 2 Dose Expansion: ABBV-514 + Budigalimab Experimental Treatment 2 Interventions

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

Group II: Part 2 Dose Expansion: ABBV-514 Experimental Treatment 1 Intervention

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

Group III: Part 1 Dose Escalation: ABBV-514 + Budigalimab Experimental Treatment 2 Interventions

Participants will receive ABBV-514 in combination with budigalimab.

Group IV: Part 1 Dose Escalation: ABBV-514 Experimental Treatment 1 Intervention

Participants will receive 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

Findings from Research

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]

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]

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]

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]

References

1. United States 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. [2021]

2. England 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

4. 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]

5. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

8. United States 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. [2023]