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

• 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 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 zongertinib in earlier stages of disease in resectable HER2 (ERBB2)-mutant non-small cell lung cancer (NSCLC), where new targeted treatment options are still needed³

Ingelheim, Germany and Ridgefield, Conn - 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.^1,8

Delta-like canonical Notch ligand 3 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 zongertinib 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 zongertinib 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 zongertinib 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).^12,13,14 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.¹ In 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 zongertinib

Zongertinib  is an irreversible tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 while sparing wild-type EGFR, thereby minimizing associated toxicities.^16,17 Zongertinib is approved in the U.S., China, Hong Kong and Japan as the first once-daily orally administered targeted therapy for adult patients with HER2 (ERBB2)-mutant advanced non-small cell lung cancer. Zongertinib is not approved in other markets. 

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 zongertinib 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 zongertinib 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/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 www.boehringer-ingelheim.com. 

References 

1. ClinicalTrials.gov. DAREON®-Lung-1 (NCT07472517). Accessed June 2026.
2. ClinicalTrials.gov. DAREON®-NEC-1 (NCT07544654). Accessed June 2026.
3. ClinicalTrials.gov. Beamion LUNG-3 (NCT07195695). Accessed June 2026.
4. Xu J, Li Y, Xu B, Lian J, Lu H. Clinical characteristics and survival outcomes of extrapulmonary neuroendocrine carcinomas: a retrospective study. Front Endocrinol (Lausanne). 2025;16:1635630. Published 2025 Oct 27. doi:10.3389/fendo.2025.1635630
5. 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  
6. 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
7. 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 
8. 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 
9. 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  
10. 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. 
11. 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.
12. 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)
13. 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.
14. ClinicalTrials.gov. DAREON®-7 (NCT06132113). Accessed June 2026.
15. ClinicalTrials.gov. DAREON®-5 (NCT05882058). Accessed June 2026.
16. HERNEXEOS Prescribing Information.
17. Wilding B, Woelflingseder L, Baum A, et al. Zongertinib (BI 1810631), an Irreversible HER2 TKI, Spares EGFR Signaling and Improves Therapeutic Response in Preclinical Models and Patients with HER2-Driven Cancers. Cancer Discov. 2025;15(1):119-138. doi:10.1158/2159-8290.CD-24-0306
18. ClinicalTrials.gov. Beamion LUNG-2 (NCT06151574). Accessed June 2026.

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