Boehringer Ingelheim has launched three Phase III cancer trials evaluating obrixtamig in DLL3-positive neuroendocrine cancers and zongertinib in early-stage HER2-mutant NSCLC.
Written By: Fariha Sameen, PharmD
Reviewed By: Pharmacally Editorial Team
Boehringer Ingelheim has initiated three Phase III clinical trials across its oncology portfolio, advancing investigational therapies obrixtamig and zongertinib in cancers with limited treatment options. The newly launched studies include DAREON®-Lung-1 in extensive-stage small cell lung cancer (SCLC), DAREON®-NEC-1 in extrapulmonary neuroendocrine carcinoma (epNEC), and Beamion LUNG-3 in resectable HER2 (ERBB2)-mutant non-small cell lung cancer (NSCLC).
The trials reflect a broader effort to expand precision medicine by matching therapies to specific tumor biomarkers and moving targeted treatments into earlier disease settings where recurrence rates remain high.
Targeting DLL3 in Aggressive Neuroendocrine Cancers
Obrixtamig is an investigational DLL3/CD3 bispecific T-cell engager that redirects the body’s immune cells toward DLL3-expressing cancer cells. DLL3 is highly expressed in several aggressive neuroendocrine tumors, including SCLC and epNEC, while showing limited expression in healthy tissues.
Small cell lung cancer remains one of the most aggressive forms of lung cancer, with rapid disease progression and poor long-term survival despite current therapies. Extrapulmonary neuroendocrine carcinoma is a rare and historically under-researched cancer with few therapeutic advances over recent decades.
The Phase III DAREON®-Lung-1 study (NCT07472517) is evaluating obrixtamig combined with atezolizumab and chemotherapy as a first-line treatment for patients with extensive-stage SCLC. Meanwhile, DAREON®-NEC-1 (NCT07544654) is investigating obrixtamig plus carboplatin and etoposide versus standard chemotherapy alone in patients with DLL3-positive unresectable locally advanced or metastatic epNEC.
These studies will determine whether adding DLL3-targeted immunotherapy can improve outcomes compared with current standard treatment approaches in biomarker-selected patient populations.
Beamion LUNG-3 Moves Zongertinib into Early-Stage NSCLC
Boehringer has also launched Beamion LUNG-3 (NCT07195695), a global randomized Phase III trial evaluating zongertinib as adjuvant monotherapy in patients with stage II-IIIB HER2-mutant NSCLC following complete surgical resection.
The study will compare zongertinib with physician’s choice standard of care and assess disease-free survival as the primary endpoint. Eligible patients must have received either neoadjuvant or adjuvant therapy before enrollment.
Zongertinib is an irreversible HER2-selective tyrosine kinase inhibitor that minimizes inhibition of wild-type EGFR, potentially reducing EGFR-related toxicities. The drug is already approved in the United States, China, Hong Kong, and Japan for adults with HER2-mutant advanced NSCLC.
Strategic Focus on Biomarker-Driven Oncology
Lykke Hinsch Gylvin, MD, Chief Medical Officer at Boehringer Ingelheim, emphasized the need for more treatment options in aggressive cancers and highlighted the company’s strategy of advancing biomarker-informed therapies into later-stage development and earlier treatment settings.
The launch of these Phase III programs marks a significant expansion of Boehringer’s precision oncology portfolio, which combines targeted therapies with next-generation immunotherapies such as T-cell engagers.
Clinical Path Forward
Patient enrollment is underway across all three studies. Positive outcomes could establish obrixtamig as a new biomarker-driven treatment option for DLL3-positive neuroendocrine cancers and extend zongertinib’s role beyond advanced disease into the adjuvant treatment setting for early-stage HER2-mutant NSCLC.
The trials represent important late-stage development milestones and could help redefine treatment strategies in several high-unmet-need cancer populations.
What This Could Mean for Patients
People diagnosed with small cell lung cancer (SCLC), extrapulmonary neuroendocrine carcinoma (epNEC), or HER2-mutant non-small cell lung cancer often have limited treatment options and face a high risk of disease progression or recurrence. These new Phase III studies are testing whether more personalized treatments can improve outcomes by targeting specific biomarkers found in cancer cells. If successful, obrixtamig could provide a new treatment option for patients with aggressive DLL3-positive cancers, while zongertinib could help reduce the risk of cancer returning after surgery in patients with early-stage HER2-mutant lung cancer. Although these therapies are still under investigation and not yet approved for these uses, positive trial results could lead to more effective and tailored treatment choices in the future.
Reference
Three Phase 3 trials in hard-to-treat cancers initiated | Boehringer Ingelheim
About the Writer
Fariha Sameen, PharmD (LinkedIn), is a clinical pharmacy professional with hands-on experience in patient counselling, medication review, therapeutic monitoring, and clinical documentation across multiple departments. She has experience identifying and assessing drug-related problems and supporting medication safety practices. Her interests include pharmacovigilance, ADR reporting, clinical research, and medical writing focused on clear, evidence-based communication.