Navigating HER2-Mutation NSCLC: What to Know About Hernexeos

Written by Patricia Weiser, PharmD
Medically Reviewed by Beth Johnston, PharmD, BCPS on September 10, 2025
8 min read

If you or a loved one has lung cancer, you may be looking into treatment options. A new medicine you might hear about is Hernexeos (zongertinib).

The FDA approved Hernexeos in August 2025. It is an oral tablet approved to treat non-small-cell lung cancer (NSCLC) in certain people. NSCLC is the most common type of lung cancer. 

More specifically, Hernexeos is FDA-approved to treat NSCLC in advanced cases where the person has already received treatments and their tumors have abnormal gene changes, called HER2 mutations. These mutations can cause cancer cells to grow and spread more quickly. Up to 3% of people with NSCLC have HER2 mutations, which can make the cancer harder to treat. 

Hernexeos may also be used for other conditions as determined by your health care provider. Below are common questions and answers about using Hernexeos for lung cancer.

To see if Hernexeos is right for you, your health care provider will consider things like the type of lung cancer you have. They may take a tissue sample from your tumor for testing (biopsy) and review your medical history. They will also consider other medicines you take and whether you have already tried treatments for your lung cancer.

Hernexeos is FDA-approved to treat non-small-cell lung cancer (NSCLC) in adults whose cancer meets all of the following requirements:

  • The cancer cannot be removed by surgery (unresectable) or has already spread to distant parts of your body (metastatic).
  • The cancer is non-squamous, which means the cancer formed in lung cells that are not squamous cells. (Squamous cells are located in the lining of the airways in the lungs.)
  • The cancer has abnormal gene changes, known as HER2 (ERBB2) tyrosine kinase domain activating mutations.
  • The cancer has already been treated with standard cancer medicines that affect your whole body (such as pills or injections).

Before prescribing Hernexeos, your health care provider will do a special biomarker test to see if your cancer has HER2 mutations. 

Hernexeos is only approved for use in adults. It is not known if this medicine is safe or effective for children.

Some lung cancer cells have abnormal changes in their DNA called mutations. These mutations can make proteins, such as HER2, overactive. When HER2 is overactive, it sends constant signals that can make cancer cells grow and spread.

Hernexeos works by blocking HER2, which helps stop those signals. By shutting down this signaling pathway, Hernexeos slows down how quickly lung cancer cells with HER2 mutations grow and multiply. It may also shrink tumors that have HER2 mutations.

Hernexeos is a tablet that you take by mouth, either with or without food. Since Hernexeos can cause nausea as a side effect, your health care provider may recommend taking it with food. Swallow the tablets whole with water. Do not split, crush, or chew the tablets.

To start treatment, the recommended dosage of Hernexeos depends on your body weight:

  • If you weigh less than 90 kilograms (about 198 pounds), the typical dosage is 120 milligrams (mg) once daily.
  • If you weigh 90 kilograms or more, the usual dose is 180 mg once daily.

You will likely take Hernexeos once daily unless your oncologist tells you to stop, such as if the medicine is no longer working or you have side effects that make it unsafe to continue.

If you get certain side effects, your oncologist may pause your treatment or lower your dose. For example, your doctor may lower your dose from 180 mg to 120 mg, or from 120 mg to 60 mg. If your doctor lowered your dose to 60 mg and this dose is causing problems, your doctor may recommend stopping Hernexeos.

Always follow your prescriber’s exact instructions as your dose may be changed based on your weight, side effects, and any other medicines you are taking.

A clinical trial called Beamion LUNG-1 was done to see if Hernexeos is safe and effective for the treatment of non-squamous non-small-cell lung cancer (NSCLC). To join, adults with NSCLC had to meet the following requirements:

  • Their lung cancer had already spread to other areas of the body or brain (metastatic) or could not be removed by surgery (unresectable).
  • Their cancer had abnormal gene changes known as HER2 mutations.
  • They had already received treatments for their cancer.
  • They did not have a history of inflammatory lung problems, such as interstitial lung disease or pneumonitis. 

In this trial, people took Hernexeos once daily. They kept taking the treatment as long as it was working and the side effects were manageable. Treatment stopped if the cancer got worse or serious side effects happened. 

The effectiveness of Hernexeos was evaluated in a group of 71 adults who took part in the Beamion LUNG-1 trial. Here are some details about these people and what their cancer was like before starting Hernexeos:

  • Age: The average age was 62, with an age range of 30 to 80. 
  • Sex: Most were female (70%) and the rest were male (30%). 
  • Race and ethnicity: 55% were Asian, 35% were White, none were Black or African American, and 10% had unknown race data; 1.4% were of Hispanic or Latino ethnicity.
  • Daily activity status: 39% had no cancer-related symptoms affecting daily activity (ECOG score of 0), while most (61%) had mild symptoms (ECOG score of 1).
  • Smoking history: 65% had never smoked.
  • Cancer spread: All of the people (100%) had metastatic NSCLC, meaning the disease had spread from the lungs to distant areas of the body. In 37% of the people, the cancer had already spread to the brain. 
  • Past treatments: All of the people tried at least one lung cancer treatment in the past before joining the trial, including platinum chemotherapy and/or an immune checkpoint inhibitor (anti-PD-1/PD-L1 therapy). In this group, no one had been treated with medicines that specifically target HER2, such as HER2-blocking tyrosine kinase inhibitors or HER2 antibody-drug conjugates. 

The effectiveness of Hernexeos was also evaluated in a second group of 34 adults who took part in the Beamion LUNG-1 trial. This group was similar to the first, except the cancer had already spread to the brain in 74% of people, and they had already received multiple previous treatments including both platinum chemotherapy and a HER2-targeted antibody-drug conjugate. 

The main goal of the Beamion LUNG-1 trial was to see how well Hernexeos worked for non-small-cell lung cancer (NSCLC). The researchers measured how well the treatment worked by looking at the objective response rate (ORR), which shows how many people had their tumors shrink or disappear on scans. They also tracked the duration of response (DOR), which is how long the tumors stayed smaller before growing again.

The Beamion LUNG-1 trial found that Hernexeos is an effective treatment for HER2-mutated NSCLC, based on the main results of the study. Your results may be different from what was seen in studies.

Out of a group of 71 adults (with no past HER2-targeted treatments; see other details above), the objective response rate was 75%:

  • 69% of people had a partial response, meaning that scans showed that their tumors got smaller.
  • 6% of people had a complete response, meaning their cancer could no longer be seen on scans.
  • Of the people who saw a response:
    • 31 people (58%) had their tumors stay smaller for at least six months before growing again. 
    • The duration of response (DOR) lasted anywhere from 1.3 months to more than 15 months; some people’s responses were still ongoing when the results were analyzed. 

Out of 34 adults (with past HER2-targeted treatment; see other details above), 44% had an objective response:

  • About 41% of people had a partial response.
  • Nearly 3% had a complete response.
  • Among people who saw a response, 27% had their tumors stay smaller for at least six months before growing again. 
    • The median duration of response (DOR) was 5.4 months. (This means of all the DOR times from smallest to largest, 5.4 months was the middle value.)

The FDA granted accelerated approval to Hernexeos for certain adults with advanced NSCLC with HER2 mutations. This early approval was based on how many people responded to Hernexeos and how long the responses lasted. But more studies are still ongoing to confirm whether Hernexeos can help people live longer. 

Hernexeos can interact with other medicines, herbs, and supplements. The following information describes the types of drug interactions that can happen with Hernexeos and how these interactions are typically managed. 

  • Strong CYP3A4 inducers. Some medicines are called strong inducers of an enzyme called CYP3A4. This enzyme plays a role in how your body processes many medicines, including Hernexeos. Strong inducers of CYP3A4 can interact with Hernexeos and affect how well it works. One example is carbamazepine (Carbatrol, Tegretol, and others), which is a medicine commonly used to treat seizures or nerve pain. 
    • Ideally, you will not take both Hernexeos and a strong CYP3A4 inducer. 
    • If you must take one of these medicines, your health care provider may need to increase your dose of Hernexeos. After you stop the other medicine, your dose may be lowered back to your original amount. 
  • BCRP substrates. Hernexeos can block a protein in the body called BCRP. This protein helps move certain substances (substrates), including certain medicines, in or out of cells. Taking Hernexeos and a BCRP substrate together can increase the levels and side effects of the BCRP substrate. One example is rosuvastatin (Crestor), which is a medicine to lower cholesterol.
    • Ideally, you will not take both Hernexeos and a BCRP substrate.
    • If you must take one of these medicines, your health care provider may need to adjust your dose of the BCRP substrate and/or monitor you more closely for side effects.  

This is not a complete list of drug interactions. Do not change your dosage or stop any medicines on your own. Your health care team will let you know how to safely manage any drug interactions.

To help prevent interactions, give your oncologist a full list of all the prescription medications, over-the-counter medicines, vitamins, and supplements you use before you start Hernexeos. Also check with your prescriber or pharmacist before taking any new medicines or supplements while taking Hernexeos. Be sure to keep your medication list up to date and bring it to every appointment so your health care team can check for interactions and help you stay safe while taking Hernexeos.

Cost assistance programs are available from Boehringer Ingelheim, the manufacturer of Hernexeos. These programs may reduce the amount you pay. Whether you qualify to enroll depends on what type of insurance you have or if you are uninsured. Visit www.hernexeos.com for more information about Hernexeos copay savings and patient assistance programs.

 You can also contact the drugmaker at 855-297-5903 to connect with a representative for financial support information and other resources.