Boehringer Ingelheim accelerates precision oncology research with initiation of three Phase III trials in hard-to-treat cancers

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Jun 22, 2026, 07:00 ET

Boehringer Ingelheim is committed to improving outcomes for people facing aggressive cancers where there are currently few treatment options
DAREON®-Lung-1 and DAREON®-NEC-1 will evaluate obrixtamig, Boehringer's immunoglobin G (IgG)-like bispecific T-cell engager, as a DLL3 biomarker-informed approach designed to help identify patients and inform treatment decisions for small cell lung cancer (SCLC) and extrapulmonary neuroendocrine carcinoma (epNEC)^1,2
Beamion LUNG-3 will explore HERNEXEOS® (zongertinib tablets) in earlier stages of disease in resectable HER2 (ERBB2)-mutant non-small cell lung cancer (NSCLC), where new targeted treatment options are still needed³

RIDGEFIELD, Conn. and INGELHEIM, Germany, June 22, 2026 /PRNewswire/ -- Boehringer Ingelheim is advancing biomarker-informed approaches and extending precision care across multiple cancers and stages of disease, reinforcing its ambition to bring unprecedented impact and improve long-term outcomes where unmet need remains high.^4,5,6 The company has initiated two Phase III clinical trials within the DAREON® program: DAREON®-Lung-1 in small cell lung cancer (SCLC) and DAREON®-NEC-1 in extrapulmonary neuroendocrine carcinoma (epNEC). In parallel, the Phase III Beamion LUNG-3 trial has been initiated in HER2 (ERBB2)-mutant non-small cell lung cancer (NSCLC).^4,5,6

"People living with aggressive cancers often face a shortage of treatment choices," said Lykke Hinsch Gylvin, MD, Chief Medical Officer, Boehringer Ingelheim. "With the launch of these trials, we are advancing our precision oncology ambitions to move targeted therapies into earlier treatment lines and bring biomarker-informed science into late-stage development. By focusing on the biology of each tumor, we aim to give patients facing cancer more precise treatment options with the goal of improving outcomes where the need is greatest."

Biomarker-informed approaches: DLL3

The two DAREON® Phase III trials mark a pivotal step for obrixtamig, Boehringer's investigational DLL3/CD3 T-cell engager, and for the company's broader biomarker strategy in aggressive neuroendocrine carcinomas (NECs) such as SCLC and epNEC. People with SCLC, the most aggressive type of lung cancer, often face short-lived therapeutic benefit and poor survival with existing approaches.^5,7 EpNEC is a historically under-researched cancer for which survival outcomes have not improved in decades. For those living with these cancers, treatment options are limited and significant unmet needs persist.^7,8

Delta-like canonical Notch ligand 3 (DLL3) is expressed on tumor cells in SCLC and epNEC while largely absent from non-cancerous cells. This makes it a potential predictive biomarker that could help to redefine treatment strategies for these aggressive cancers.^9,10 DAREON®-Lung-1 and DAREON®-NEC-1 are designed to test whether the addition of obrixtamig, a DLL3 targeted T-cell engager, can improve outcomes in biomarker-informed patient populations versus the current standard of care.^1,2 Together, the studies aim to position obrixtamig as part of a broader shift toward more personalized and potentially more transformative treatment approaches in these aggressive NECs.

Precision oncology in earlier stages: HER2

In addition, the company is investigating HERNEXEOS® (zongertinib tablets) in earlier stages of disease with the initiation of Beamion LUNG-3. This global, randomized Phase III trial will study the efficacy and safety of HERNEXEOS as adjuvant monotherapy compared with physician's choice standard of care in patients with stage II-IIIB HER2 (ERBB2)-mutant NSCLC who have undergone complete surgical resection and have received either neoadjuvant or adjuvant therapy.³ The study is designed to evaluate whether HERNEXEOS can improve disease-free survival compared to standard of care following surgery, addressing the significant risk of recurrence after curative-intent treatment.¹¹ Beamion LUNG-3 reflects the company's focus on advancing targeted therapies earlier in the treatment pathway, where effective targeted adjuvant treatment options are not available.¹² This trial extends the investigation of zongertinib to early stage disease.³

Expanding the oncology portfolio

Boehringer Ingelheim continues to expand its portfolio of precision oncology approaches that combine targeted therapies for biomarker-defined populations with innovative strategies to both activate and direct the immune system. This includes next-generation immunotherapies such as T-cell engagers, alongside complementary modalities that aim to enhance anti-tumor responses and address tumor-intrinsic drivers of disease. By integrating these approaches, the company aims to expand treatment options for people facing cancers with high unmet medical need.

About obrixtamig

Obrixtamig is an investigational novel Immunoglobin G (IgG)-like bispecific T-cell engager designed to bind concomitantly to DLL3 on tumor cells and CD3 on T-cells, potentially resulting in destruction of tumor cells by the body's own immune system. Obrixtamig is being evaluated in multiple, ongoing clinical trials, including a Phase I trial in combination with atezolizumab and chemotherapy in extensive-stage small-cell lung cancer (ES-SCLC) patients (DAREON®-8), a Phase Ib study to investigate obrixtamig in combination with the current SoC (carboplatin + etoposide) as 1L treatment for patients with DLL3-positive NEC, including epNEC (DAREON®-7), and a Phase II trial in patients with relapsed/refractory DLL3-high extrapulmonary neuroendocrine carcinomas (epNEC) (DAREON^®-5).^13,14,15 The Phase III clinical development program includes DAREON®-LUNG-1, which evaluates obrixtamig in combination with atezolizumab plus chemotherapy vs. atezolizumab plus chemotherapy for first-line use in patients with ES-SCLC.¹In addition, DAREON®-NEC-1 is evaluating obrixtamig in combination with current SoC (carboplatin and etoposide) vs. SoC alone as first-line therapy in patients with DLL3-positive unresectable locally advanced or metastatic epNEC.²

In order to tackle hard-to-treat cancers, Boehringer is drawing on innovation enabled through collaboration. The company is developing obrixtamig through a long-term partnership with Oxford BioTherapeutics (OBT), using OBT's OGAP® platform to identify novel target opportunities for new immunotherapies harnessing its investigational T-cell engager, investigational cancer vaccine and exploratory oncolytic virus platforms.

About HERNEXEOS® (zongertinib tablets)

HERNEXEOS® (zongertinib tablets) is an irreversible tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 (ERBB2).¹⁶ HERNEXEOS has been approved by the U.S. Food and Drug Administration (FDA) as the first orally administered, targeted therapy for adult patients with HER2 (ERBB2)-mutant advanced non-small cell lung cancer.¹⁶

Comprehensive biomarker testing using next generation sequencing determines a patient's eligibility for treatment with HERNEXEOS by identifying HER2 (ERBB2)-mutant advanced NSCLC.^16,17

The treatment is being evaluated in ongoing trials, across a range of earlier stages and advanced solid tumors with HER2 alterations. Beamion LUNG-2 is an ongoing Phase III controlled study evaluating HERNEXEOS as a first-line treatment for patients with advanced NSCLC that has HER2 tyrosine kinase domain mutations (NCT06151574).¹⁸ Beamion LUNG-3 is a Phase III clinical trial investigating HERNEXEOS as an adjuvant monotherapy in patients with early-stage, resectable NSCLC (Stage II-IIIB) with HER2 (ERBB2)-mutations (NCT07195695).³

About Boehringer Ingelheim in oncology

We have a clear aspiration – to transform the lives of people facing cancer by delivering unprecedented impact, with the ultimate goal to redefine standards of care. Boehringer Ingelheim's long-term commitment to scientific innovation is reflected by the company's robust pipeline of cancer cell-directed and immuno-oncology investigational therapies, as well as in smart combinations of these approaches. In everything we do, we focus on people — not just data — working alongside them to develop solutions that truly meet their needs and help move cancer into the background of their lives. This drives our research approach, drawing on diverse minds and a long-term perspective to address the needs of people facing cancer today and for generations to come. Read more at https://www.boehringer-ingelheim.com/us/human-health/cancer.

About Boehringer Ingelheim

Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry's top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. Our approximately 54,300 employees serve over 130 markets to build a healthier and more sustainable tomorrow. Learn more at https://www.boehringer-ingelheim.com/us.

What is HERNEXEOS (zongertinib tablets)?

HERNEXEOS is a prescription medicine used to treat adults with a type of lung cancer called non–squamous non–small cell lung cancer (NSCLC) that:

cannot be removed by surgery or that has spread to other parts of your body (metastatic), and
has a certain mutation in the human epidermal growth factor receptor 2 (HER2) gene

Your healthcare provider will perform a test to make sure HERNEXEOS is right for you.

It is not known if HERNEXEOS is safe and effective in children.

IMPORTANT SAFETY INFORMATION

Before taking HERNEXEOS, tell your healthcare provider about all of your medical conditions, including if you:

have liver problems
have heart problems
have lung or breathing problems other than lung cancer
are pregnant or plan to become pregnant. HERNEXEOS can harm your unborn baby
Females who are able to become pregnant:
- Your healthcare provider will do a pregnancy test before you start treatment with HERNEXEOS
- Use an effective form of birth control (contraception) during treatment with HERNEXEOS and for 2 weeks after your last dose
- Talk to your healthcare provider about birth control methods that might be right for you during this time
- Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with HERNEXEOS
- are breastfeeding or plan to breastfeed. It is not known if HERNEXEOS passes into your breastmilk. Do not breastfeed during treatment and for 2 weeks after your last dose of HERNEXEOS

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. HERNEXEOS may affect the way other medicines work, and other medicines may affect how HERNEXEOS works.

Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.

What are the possible side effects of HERNEXEOS?

HERNEXEOS may cause serious side effects, including:

liver problems. Liver problems are common with HERNEXEOS and can be severe and life-threatening. Your healthcare provider will do blood tests to check your liver function before you start taking HERNEXEOS and during your treatment. Tell your healthcare provider right away if you develop any signs and symptoms of liver problems, including:
- yellowing of your skin or the white part of your eyes (jaundice)
- dark or brown (tea colored) urine
- pain on the upper right side of your stomach area (abdomen)
- bleeding or bruising more easily than normal
- feeling very tired
- loss of appetite
- nausea or vomiting
heart problems that may affect your heart's ability to pump blood. HERNEXEOS can cause severe heart problems. Your healthcare provider will do tests to check your heart function before you start taking HERNEXEOS and during treatment. Tell your healthcare provider right away if you have any new or worsening symptoms of heart problems, including:
- feeling like your heart is pounding or racing
- dizziness
- tiredness
- feeling lightheaded
- shortness of breath
- loss of consciousness
- coughing
- swelling of your legs, ankles, or feet
lung problems. HERNEXEOS can cause lung problems that are severe or life-threatening. Tell your healthcare provider right away if you have any new or worsening symptoms of lung problems, including trouble breathing, shortness of breath, cough, or fever

Your healthcare provider may temporarily stop, decrease your dose, or permanently stop treatment with HERNEXEOS if you have serious side effects.

The most common side effects of HERNEXEOS include:

diarrhea. HERNEXEOS can cause severe diarrhea. Tell your healthcare provider right away if you have new or worsening diarrhea
rash
liver problems
feeling tired
nausea
muscle and joint pain
upper respiratory tract infection

The most common severe abnormal blood tests include decreased white blood cell count, increased liver function tests, and decreased potassium levels.

HERNEXEOS may cause fertility problems in females and males, which may affect your ability to have children. Talk to your healthcare provider if this is a concern for you.

These are not all of the possible side effects of HERNEXEOS. Call your doctor for medical advice about side effects. For more information, ask your healthcare provider or pharmacist.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

CL-HER-100001 02.2026

Please see full Prescribing Information and Patient Information.

MPR-US-104244

References:

ClinicalTrials.gov. DAREON-Lung-1 (NCT07472517). Accessed June 2026.
ClinicalTrials.gov. DAREON-NEC-1 (NCT07544654). Accessed June 2026.
ClinicalTrials.gov. Beamion LUNG-3 (NCT07195695). Accessed June 2026.
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Plaja A, et al. Small-Cell Lung Cancer Long-Term Survivor Patients : How to Find a Needle in a Haystack?. Int J Mol Sci. 2021;22(24):13508. Published 2021 Dec 16. doi:10.3390/ijms222413508
Jeon H, Wang S, Song J, Gill H, Cheng H. Update 2025: Management of Non Small-Cell Lung Cancer. Lung. 2025;203(1):53. Published 2025 Mar 25. doi:10.1007/s00408-025-00801-x
Uprety D, Seaton R, Niroula A, Hadid T, Parikh K, Ruterbusch JJ. Trends in the incidence and survival outcomes in patients with small cell lung cancer in the United States: an analysis of the SEER database. Cancer Med. 2025;14(3):e70608. doi:10.1002/cam4.70608
Frizziero M, Chakrabarty B, Nagy B, et al. Is the morphological subtype of extra-pulmonary poorly differentiated neuroendocrine carcinoma clinically relevant? Cancers (Basel). 2021;13(16):3986
Liverani C, Bongiovanni A, Mercatali L, et al. Diagnostic and Predictive Role of DLL3 Expression in Gastroenteropancreatic Neuroendocrine Neoplasms. Endocr Pathol. 2021;32(2):309-317. doi:10.1007/s12022-020-09657-81
Wermke M, et al. Phase I Dose-Escalation Results for the Delta-Like Ligand 3/CD3 IgG-Like T-Cell Engager Obrixtamig (BI 764532) in Patients With Delta-Like Ligand 3+ Small Cell Lung Cancer or Neuroendocrine Carcinomas. J Clin Oncol 2025;43(27):3021–31.
Brandon, S. et al. Risk factors and survival associated with lung cancer recurrence after curative-intent surgery: beyond TNM pathological staging. Journal Of Thoracic Disease. 2025;17(11):10285-10297.
Hao S, Zhao S, Shi L, Zhong L, Wei H, Jiao X, Xue C. Targeting rare oncogenic mutations in resectable non-small cell lung cancer: emerging perioperative strategies. Journal of Thoracic Disease. 2026;18(2)
Peters, S, et al. DAREON®-8: updated efficacy and safety from a phase I dose-escalation/expansion trial of first-line (1L) obrixtamig plus chemotherapy and atezolizumab in extensive-stage small cell lung carcinoma (ES-SCLC). Poster presented at: American Society of Clinical Oncology Annual Meeting; May 29 – June 2, 2026; Chicago, IL.
ClinicalTrials.gov. DAREON-7 (NCT06132113). Accessed June 2026.
ClinicalTrials.gov. DAREON-5 (NCT05882058). Accessed June 2026.
HERNEXEOS Prescribing Information.
Zeng J, Ma W, Young RB, Li T. Targeting HER2 genomic alterations in non-small cell lung cancer. J Natl Cancer Cent. 2021;1(2):58-73.
ClinicalTrials.gov. Beamion LUNG-2 (NCT06151574). Accessed June 2026.