Ongoing Clinical Trials for HER2 Mutant Non-Small Cell Lung Cancer
There are currently 3 clinical trials investigating new treatments for HER2 mutant non-small cell lung cancer across Europe. These studies are testing different approaches including targeted antibody therapies and immunotherapy combinations. Trials are being conducted in multiple countries including France, Germany, Poland, Italy, Belgium, Spain, Netherlands, Austria, and Denmark, offering patients various options for accessing innovative treatments.
Clinical trial locations
- Austria
- Belgium
- Denmark
- France
- Germany
- Italy
- Netherlands
- Poland
- Spain
Study of zanidatamab in adult patients with HER2-positive solid tumors (endometrial, colorectal, head & neck, sarcoma) or HER2-mutant non-small cell lung cancer
This trial is testing zanidatamab, a novel antibody-based therapy that targets the HER2 protein found on cancer cells. The study focuses on patients with various solid tumors, including lung cancer with HER2 mutations, as well as endometrial, colorectal, head and neck cancers, and sarcoma.
Main inclusion criteria: Participants must be at least 18 years old with a confirmed diagnosis of advanced or metastatic cancer that cannot be surgically removed. The cancer must be HER2-positive or have HER2 mutations, and patients should have received at least one prior treatment that is no longer working. Additional requirements include adequate liver, kidney, and bone marrow function, good heart function with a pumping capacity of at least 50%, and the ability to perform most daily activities. Participants must also have measurable disease and a life expectancy of more than 3 months.
Main exclusion criteria: Patients cannot participate if they received HER2-directed therapy within 4 weeks before the study, have untreated or unstable brain metastases, or have had another cancer within the past 2 years. Other exclusions include severe heart conditions, active infections, known HIV or active hepatitis infections, and pregnancy or breastfeeding.
Focus of the trial: The main goal is to evaluate how well zanidatamab works in treating these different types of HER2-positive cancers. Researchers will monitor whether tumors respond to treatment by shrinking or disappearing, using regular scans to track progress and watch for side effects.
Investigational drug: Zanidatamab is administered through intravenous infusion and works by attaching to two different sites on the HER2 receptor simultaneously, creating a more effective blocking mechanism that stops cancer cell growth. This bispecific antibody represents a precision medicine approach for patients with HER2-positive cancers. Treatment may continue for up to three years, with a maximum daily dose of 2400 milligrams.
Study on Atezolizumab, Carboplatin, and Etoposide for Adults with Advanced Large-Cell Neuroendocrine Lung Cancer
This clinical trial examines a combination treatment approach for large-cell neuroendocrine carcinoma of the lung. The study tests whether adding immunotherapy to standard chemotherapy can improve patient survival.
Main inclusion criteria: Participants must be at least 18 years old with a diagnosis of locally advanced or metastatic large-cell neuroendocrine carcinoma without curative treatment options. If the cancer has mixed types, this type should represent at least 50%. Patients must not have received previous systemic therapy, although those whose cancer returned at least 6 months after completing curative treatment may participate. Other requirements include an ECOG performance status of 0 to 2, measurable disease according to specific criteria, and adequate organ function including appropriate liver enzyme levels, bilirubin, creatinine, neutrophil, and platelet counts.
Main exclusion criteria: Patients who received any cancer treatment within the last 4 weeks, have severe allergies to study drugs, active infections requiring treatment, or serious medical conditions that could interfere with the study cannot participate. Additional exclusions include pregnancy or breastfeeding, participation in another clinical trial within the past 4 weeks, history of another cancer unless in remission for at least 5 years, brain metastases that haven’t been treated and stabilized, unstable autoimmune diseases, and recent drug or alcohol abuse.
Focus of the trial: The study evaluates how well the combination of atezolizumab with platinum-based chemotherapy and etoposide works in improving survival and controlling the cancer. Researchers will monitor how long patients live after starting treatment, changes in cancer size, time until cancer starts growing again, and any side effects experienced during treatment.
Investigational drugs: Atezolizumab is an immunotherapy medication that helps the immune system recognize and attack cancer cells by blocking proteins that allow cancer cells to hide. It is combined with carboplatin or cisplatin, which are platinum-based chemotherapy drugs that damage cancer cell DNA, and etoposide, which interferes with DNA inside cancer cells to stop them from dividing. All medications are administered through intravenous infusion in treatment cycles.
Study on Trastuzumab Deruxtecan for Patients with Advanced Non-Small Cell Lung Cancer with HER2 Mutations
This trial investigates trastuzumab deruxtecan as a first-line treatment option for lung cancer with specific HER2 genetic changes. The study compares this targeted therapy against standard chemotherapy combinations.
Main inclusion criteria: Participants must be at least 18 years old with locally advanced or metastatic non-squamous non-small cell lung cancer that cannot be surgically removed. The cancer must have a specific HER2 mutation in exons 19 or 20, confirmed by tissue or blood testing. Patients should not have received any systemic therapy for their advanced or metastatic disease. Additional requirements include a heart pumping capacity of 50% or higher, measurable disease by specific criteria, adequate organ function including heart, kidney, and liver, an ECOG performance status of 0 or 1, and available tumor tissue for testing.
Main exclusion criteria: Patients without the specific HER2 exon 19 or 20 mutations cannot participate. Others excluded include those whose cancer can be removed by surgery, those without advanced or metastatic disease, patients outside the specified age range, and those not part of the specified clinical trial groups.
Focus of the trial: The study aims to determine whether trastuzumab deruxtecan is more effective than standard treatment combinations in stopping cancer growth or spread. Researchers will assess overall survival, monitor side effects, and evaluate quality of life outcomes through regular check-ups and assessments over several years.
Investigational drugs: Trastuzumab deruxtecan is an antibody-drug conjugate that combines targeted therapy with chemotherapy. It works by targeting and binding to the HER2 protein on cancer cells, delivering a chemotherapy agent directly to kill them. Participants in the comparison group receive a combination of platinum-based chemotherapy (carboplatin or cisplatin), pemetrexed (which interferes with cancer cells’ ability to use folate), and pembrolizumab (an immunotherapy that helps the immune system recognize and attack cancer cells). All medications are administered intravenously according to the study protocol.
Summary
The three ongoing clinical trials for HER2 mutant non-small cell lung cancer reflect a focused effort on developing targeted and immunotherapy-based treatment approaches. Two of the three trials specifically target HER2 mutations, highlighting the importance of this biomarker in treatment development.
Geographically, trial availability is concentrated in Western Europe, with the trastuzumab deruxtecan study having the broadest reach across nine countries including Poland, France, Germany, Italy, Belgium, Spain, Netherlands, Austria, and Denmark. France and Germany each host two different trials, providing patients in these countries with multiple research participation options.
The investigational approaches vary considerably: zanidatamab represents a novel bispecific antibody strategy, trastuzumab deruxtecan combines targeted therapy with chemotherapy in a single molecule, and atezolizumab combines immunotherapy with traditional chemotherapy. Each trial addresses different patient populations and treatment lines, from first-line therapy to options for patients who have already received treatment. This diversity provides potential opportunities for patients at various stages of their treatment journey.
