What Is Zongertinib?
Zongertinib is an investigational drug currently being studied in clinical trials. Its specific mechanism of action is not detailed in the available trial descriptions. It is being investigated for various conditions, primarily focusing on several types of cancer such as non-small cell lung cancer, esophageal adenocarcinoma, metastatic breast cancer, and metastatic gastric adenocarcinoma. It is also being studied in healthy volunteers and individuals with liver diseases to understand its safety and how it is processed by the body. A total of 16 clinical trials involving 2,931 participants have been conducted or are ongoing for zongertinib. The majority of these studies are sponsored by Boehringer Ingelheim, with one trial sponsored by MedSIR.
Uses and Conditions Under Study
Zongertinib is currently being investigated across a range of conditions, primarily focusing on various cancers.
- Cancers: Zongertinib is being studied for several types of cancer. This includes non-small cell lung cancer, specifically the non-squamous subtype, in 2 clinical trials. It is also being investigated for cancers of the digestive system, such as esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, each in 1 trial. Metastatic gastric adenocarcinoma, a type of stomach cancer that has spread, is also a focus in 1 trial. For breast cancer, zongertinib is being studied in patients with hormone receptor positive / HER2-negative breast cancer and metastatic breast cancer, each in 1 trial. Additionally, it is being explored in cancers with a specific HER2 mutation and for general neoplasm metastasis, each in 1 trial, suggesting a broad potential application in oncology.
- Healthy Volunteers: A significant portion of the research, with 9 trials, involves healthy volunteers. These studies are crucial for understanding how zongertinib is absorbed, distributed, metabolized, and excreted by the body, as well as for assessing its safety profile in individuals without underlying conditions.
- Liver Diseases: Zongertinib is also being studied in individuals with liver diseases in 1 trial. This research helps determine how liver impairment might affect the drug's processing and dosage requirements, ensuring safe administration for patients with varying liver functions.
Dosing
Zongertinib has been studied as an oral medication, primarily in a film-coated tablet form. One specific dosage strength mentioned in trials is 120 mg, taken orally once daily.
Clinical trials have explored zongertinib both as a standalone treatment and in combination with other medications. These combinations include, but are not limited to:
- Fulvestrant
- Cisplatin or carboplatin and pemetrexed (with or without pembrolizumab)
- Trastuzumab emtansine or trastuzumab deruxtecan
- Trastuzumab (with or without capecitabine)
- mFOLFOX6 (with or without trastuzumab)
- Zanidatamab
Additionally, studies have investigated how zongertinib interacts with other drugs like carbamazepine and itraconazole. Research has also been conducted to understand the drug's behavior in specific populations, such as individuals with mild or moderate hepatic impairment (Child-Pugh A and B), compared to those with normal hepatic function. Studies have also assessed the impact of food on zongertinib absorption (fed versus fasting states). No specific pediatric dosing information is available from the provided trial data.
Side Effects
The clinical trials provided for Zongertinib primarily focused on how the drug is absorbed, distributed, metabolized, and eliminated by the body in healthy volunteers. These studies (NCT05833139, NCT05879991, NCT06028464, NCT06075277, NCT06360081) did not report specific side effects or adverse events. Therefore, information regarding the frequency and types of side effects associated with Zongertinib is not available from these pharmacokinetic studies.
Clinical Trial Results
Studies have investigated how Zongertinib is handled by the body, including its absorption, metabolism, and excretion, as well as how it interacts with other medications and food. These trials were conducted in healthy men or healthy people.
How Zongertinib is Processed by the Body
A study (NCT05879991) explored how Zongertinib is taken up and processed. The results showed that a significant amount of the administered dose, approximately 93.8%, was excreted from the body through urine and feces over time. The total amount of Zongertinib in the blood (AUC0-tz) was 14,100 hour*nanomole/Liter, with a peak level in the blood (Cmax) of 1,160 nanomole/Liter.
Interaction with Itraconazole
A study (NCT05833139) examined the effect of itraconazole, an antifungal medication, on Zongertinib levels. When Zongertinib was taken with itraconazole, the total amount of Zongertinib in the blood (AUC0-∞) increased to 4,255 Nanomoles * hour per Liter, compared to 3,014 Nanomoles * hour per Liter when Zongertinib was taken alone. Similarly, the peak level of Zongertinib in the blood (Cmax) was higher at 175 Nanomoles per Liter with itraconazole, versus 138 Nanomoles per Liter when taken alone.
Interaction with Carbamazepine
Another study (NCT06028464) investigated how carbamazepine, an anti-seizure medication, influences Zongertinib levels. Taking Zongertinib with carbamazepine significantly decreased the amount of Zongertinib in the blood. The total amount of Zongertinib in the blood (AUC0-∞) was 4,500.05 hour * nanomole / liter when taken with carbamazepine, compared to 12,334.87 hour * nanomole / liter when Zongertinib was taken alone. The peak level in the blood (Cmax) also decreased from 914.01 nanomole / liter when taken alone to 515.84 nanomole / liter with carbamazepine.
Effect of Food on Absorption
A trial (NCT06075277) assessed how food affects the absorption of Zongertinib. When Zongertinib was taken with food, the total amount in the blood (AUC0-∞) was 59,986.25 hour*nanomol/Liter, which was higher than when taken in a fasted state (47,594.57 hour*nanomol/Liter). The peak level in the blood (Cmax) also increased from 3,700.37 nanomol/Liter when fasted to 4,666.87 nanomol/Liter when taken with food.
Comparison of Tablet Formulations
A study (NCT06360081) compared two different tablet formulations of Zongertinib. The results showed that the total amount of Zongertinib in the blood over 72 hours (AUC0-72h) was very similar for both the reference treatment (13,463.07 hours*nanomole/Liter) and the test treatment (13,448.03 hours*nanomole/Liter). The peak level in the blood (Cmax) was also comparable, with 1,126.11 nanomole/Liter for the reference and 1,135.49 nanomole/Liter for the test treatment. The time to reach peak concentration (Tmax) was slightly different, with a median of 2.01 hours for the reference and 2.50 hours for the test treatment.
Currently Recruiting Trials
Zongertinib is currently being investigated in several clinical trials for various conditions. These studies aim to understand its effects, safety, and how it interacts with other treatments. Boehringer Ingelheim is the sponsor for these trials.
One study, NCT07649941, is a Phase 1 trial involving healthy men. It aims to determine how the drug bosentan affects the amount of zongertinib in the blood. This study is recruiting 16 participants.
For individuals with advanced non-small cell lung cancer (NSCLC) with HER2 mutations, the Beamion 44 study (NCT07486817) is a Phase 2 trial. It is testing how well zongertinib is tolerated when combined with chemotherapy, with or without pembrolizumab. This study is open to adults with HER2-mutant non-squamous NSCLC who have not received prior treatment for their advanced or metastatic lung cancer, and aims to enroll 60 people.
Another important study for NSCLC is Beamion LUNG-3 (NCT07195695), a Phase 3 trial. This study compares zongertinib to standard adjuvant treatment in adults with completely resected Stage II-IIIB NSCLC whose tumors have activating HER2 tyrosine kinase domain mutations. The goal is to see if zongertinib, an oral HER2-targeted treatment, can improve outcomes. This trial plans to enroll 400 participants.
The Beamion PANTUMOR-1 study (NCT06581432) is a Phase 2 trial for people with advanced cancers that have HER2 alterations and for whom previous treatments were not successful. This study is investigating whether zongertinib helps these patients. It is open to adults aged 18 and over and has an enrollment target of 430 participants.
Finally, the Beamion BCGC-1 study (NCT06324357) is a Phase 1/Phase 2 trial exploring zongertinib alone and in combination with other treatments for various types of HER2-positive cancer that has spread. This includes metastatic breast cancer, gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, esophageal adenocarcinoma, and colorectal cancer. Participants must have HER2 aberrations and prior unsuccessful treatment. This comprehensive study aims to enroll 768 adults.
Where to Participate
Clinical trials for zongertinib are actively recruiting across a wide geographic area, with 62 sites located in 54 cities and 27 states. This broad reach helps ensure diverse participation in the studies.
The top locations with the most recruiting sites include:
- New York, New York (5 sites)
- Los Angeles, California (4 sites)
- Fairfax, Virginia (4 sites)
- Houston, Texas (4 sites)
- Santa Monica, California (2 sites)
- Portland, Oregon (2 sites)
- New Haven, Connecticut (2 sites)
- Indianapolis, Indiana (2 sites)
- Chicago, Illinois (2 sites)
- Nashville, Tennessee (2 sites)
General eligibility for these trials requires participants to be between 18 and 55 years of age. Both men and women are eligible to participate, and some studies specifically seek healthy volunteers. Children are not eligible for these particular studies.
Development Timeline
The journey of zongertinib in clinical development began on May 14, 2021, with its first trial. Since then, the program has expanded significantly, with the latest trial projected to conclude on June 16, 2026. Boehringer Ingelheim has been the primary sponsor, leading 15 of the 16 total trials, with one trial sponsored by MedSIR.
Across these 16 trials, a total of 2,931 participants have been or are being enrolled. The development has progressed through various phases, with 10 trials in Phase 1, 3 in Phase 2, and 2 in Phase 3, alongside one combined Phase 1/Phase 2 study.
Initially, zongertinib's development focused on conditions such as IBS-C and hyperphosphatemia. However, the pipeline quickly expanded to address a broader range of serious conditions. This strategic expansion now includes various cancers, such as Esophageal Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, HER2 Mutation, Hormone Receptor Positive / HER2-negative Breast Cancer, Liver Diseases, Metastatic Breast Cancer, Metastatic Gastric Adenocarcinoma, Neoplasm Metastasis, Non-small Cell Lung Cancer, Advanced Breast Cancer, Solid Tumours, and Colorectal Cancer, reflecting a growing focus on oncology.