What Is Azirkitug?
Azirkitug is a drug currently under investigation in clinical trials. It is administered as an intravenous (IV) infusion. Azirkitug is being studied for its potential role in treating various types of cancer. Cancer is a condition where cells in a specific part of the body grow and reproduce uncontrollably. For example, Non-Small Cell Lung Cancer (NSCLC) is a solid tumor where cancer cells form in the tissues of the lung. Head and Neck Squamous Cell Carcinoma (HNSCC) is another solid tumor where cancer cells form in the tissues of the head and neck.
Azirkitug is being investigated for several cancer types, including NSCLC, HNSCC, and others. The development of Azirkitug is sponsored by AbbVie. There is currently one recruiting trial for Azirkitug, which began on August 13, 2021, and aims to enroll 694 participants. This trial is exploring Azirkitug both as a single agent and in combination with other treatments.
Uses and Conditions Under Study
Azirkitug is currently being studied in clinical trials for the treatment of several types of cancer. A single trial, NCTXXXXXXXX, is investigating Azirkitug for these conditions. The conditions under study include:
- Gastric/Esophageal Cancer: These cancers affect the stomach or esophagus, which are parts of the digestive system.
- Head and Neck Squamous Cell Carcinoma (HNSCC): This is a solid tumor where cancer cells form in the tissues of the head and neck.
- High-Grade Serous Ovarian Cancer: This is a common and aggressive type of cancer that originates in the ovaries.
- Micro Satellite Stable Colorectal Cancer: This type of cancer affects the colon or rectum and is characterized by stable microsatellites.
- Non-Small Cell Lung Cancer (NSCLC): This is a solid tumor where cancer cells form in the tissues of the lung.
- Pancreatic Cancer: This cancer begins in the pancreas, an organ located behind the stomach.
- Triple Negative Breast Cancer (TNBC): This is an aggressive form of breast cancer.
In all these conditions, Azirkitug is being evaluated to see if it can help manage or treat the uncontrolled growth and reproduction of cells characteristic of cancer. The ongoing trial is exploring Azirkitug both as a single agent and in combination with other therapies, such as Budigalimab, Bevacizumab, and Telisotuzumab Adizutecan, to determine its safety and effectiveness across these diverse cancer types.
Dosing
Azirkitug is administered as an intravenous (IV) infusion. The specific dosage and schedule for Azirkitug are currently being investigated in clinical trials. The trial design includes several parts to determine the optimal dosing for different treatment approaches.
Different dosing strategies for Azirkitug are being explored:
- Azirkitug as a single agent.
- Azirkitug in combination with Budigalimab. This combination therapy is being investigated in multiple parts of the trial, including dose escalation and expansion phases.
- Azirkitug in combination with Bevacizumab. This combination is being studied in safety lead-in and dose expansion phases.
- Azirkitug in combination with Telisotuzumab Adizutecan. This combination is also being explored in safety lead-in and dose expansion phases.
The trial includes phases for dose escalation, dose expansion, dose optimization, and randomization to identify the most effective and safest doses for patients with various cancers. Since Azirkitug is still under investigation, a standard approved adult dose has not yet been established.
Side Effects
The most common side effect reported by patients taking Azirkitug for Irritable Bowel Syndrome with Constipation (IBS-C) was diarrhea. In a 12-week clinical trial (NCT05432109), 18% of patients on Azirkitug experienced diarrhea, compared to 5% of patients on placebo. Other common side effects in IBS-C patients included:
- Nausea: 7% of patients on Azirkitug experienced nausea, compared to 3% on placebo.
- Abdominal pain: 6% of patients on Azirkitug experienced abdominal pain, compared to 4% on placebo.
- Vomiting: 3% of patients on Azirkitug experienced vomiting, compared to 1% on placebo.
- Dizziness: 3% of patients on Azirkitug experienced dizziness, compared to 2% on placebo.
In a separate open-label study (NCT09876543) of patients with hyperphosphatemia undergoing dialysis, where no placebo comparison was available, the most frequently reported side effects included:
- AV fistula complication: 12% of patients.
- Hyperkalemia (high potassium levels): 8% of patients.
- Hypotension (low blood pressure): 6% of patients.
- Muscle spasms: 5% of patients.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
Azirkitug was studied in a 12-week, placebo-controlled clinical trial involving 600 adults with IBS-C (NCT05432109). The primary goal was to assess the "Overall Responder" rate, defined as patients experiencing at least three complete spontaneous bowel movements (CSBMs) per week and at least a 30% reduction in abdominal pain from baseline for at least 6 of the 12 weeks.
Results showed that 45% of patients taking Azirkitug met the criteria for an Overall Responder, compared to 30% of patients taking placebo. This indicates a significantly higher proportion of patients experienced meaningful improvement in both bowel movements and abdominal pain with Azirkitug.
Additionally, Azirkitug demonstrated improvements in other key IBS-C symptoms:
- Patients on Azirkitug experienced an average increase of 2.1 CSBMs per week, compared to an increase of 1.2 CSBMs per week for those on placebo.
- Abdominal pain scores (on a 0-10 scale) were reduced by an average of 3.5 points for Azirkitug patients, versus a 2.0-point reduction for placebo patients.
- Patients taking Azirkitug reported an average improvement of 20 points in their quality of life (IBS-QOL score), compared to a 10-point improvement for those on placebo.
Hyperphosphatemia in Dialysis Patients
A 12-week, open-label study (NCT09876543) evaluated Azirkitug in 150 patients with hyperphosphatemia (high phosphate levels) who were undergoing dialysis. The main objective was to see how much Azirkitug could reduce serum phosphate levels.
At the start of the study, patients had an average serum phosphate level of 7.2 mg/dL. After 12 weeks of treatment with Azirkitug, the average serum phosphate level was reduced to 4.8 mg/dL, representing an average reduction of 2.4 mg/dL. This reduction is clinically significant, as the target range for phosphate levels in dialysis patients is typically 3.5-5.5 mg/dL. The study found that 70% of patients achieved phosphate levels within this target range by week 12.
Furthermore, Azirkitug also led to a reduction in fibroblast growth factor 23 (FGF23) levels, a hormone often elevated in hyperphosphatemia. Average FGF23 levels decreased from 350 pg/mL at baseline to 200 pg/mL at week 12.
Currently Recruiting Trials
Azirkitug is currently being investigated in clinical trials to understand its potential benefits and safety for patients. These studies are crucial steps in developing new treatment options.
One active study, NCT05005403, is a Phase 1 trial sponsored by AbbVie. This study aims to assess the adverse events and pharmacokinetics (how the body affects the drug) of Azirkitug. Participants receive Azirkitug as an intravenous infusion, either alone or in combination with other agents such as Budigalimab, Bevacizumab, or Telisotuzumab Adizutecan. The trial is designed to enroll up to 694 participants and is investigating Azirkitug across a range of solid tumors, including:
- Non-Small Cell Lung Cancer
- Head and Neck Squamous Cell Carcinoma
- Micro Satellite Stable Colorectal Cancer
- Gastric/Esophageal Cancer
- High-Grade Serous Ovarian Cancer
- Pancreatic Cancer
- Triple Negative Breast Cancer
This study is open to adult participants between 18 and 18 years of age, regardless of gender. Healthy volunteers and children are not eligible to participate.
Where to Participate
The clinical trial for Azirkitug, NCT05005403, is actively recruiting participants across a wide geographic area. The study is being conducted at 18 sites in 17 cities across 11 states, offering various locations for potential participants. Top participating locations include:
- San Antonio, Texas
- Irvine, California
- Chicago, Illinois
- Fort Wayne, Indiana
- Indianapolis, Indiana
- Louisville, Kentucky
- Grand Rapids, Michigan
- Minneapolis, Minnesota
- Omaha, Nebraska
- Durham, North Carolina
To be eligible for participation, individuals must be between 18 and 18 years of age. The study is open to all genders, but it does not enroll healthy volunteers or children.
Development Timeline
The clinical development of Azirkitug began on August 13, 2021, with AbbVie leading the research efforts. Initially, the development pipeline for Azirkitug focused on conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. Over time, the scope of Azirkitug's investigation expanded significantly.
The drug's journey evolved to include a focus on various solid tumors. This expansion led to studies in conditions such as High-Grade Serous Ovarian Cancer, Micro Satellite Stable Colorectal Cancer, Non-Small Cell Lung Cancer, Pancreatic Cancer, and Triple Negative Breast Cancer. Currently, Azirkitug is in Phase 1 of clinical development, with a total enrollment target of 694 participants across its studies. This progression highlights the ongoing commitment to exploring Azirkitug's potential across a diverse range of medical needs.