DAREON ® -Lung-1: A Study in People With Advanced Small Cell Lung Cancer to Compare Obrixtamig Plus Atezolizumab, Carboplatin, and Etoposide Treatment With Standard Chemotherapy

Boehringer Ingelheim

Status and phase: Begins enrollment this month; Phase 3

Conditions: Extensive-stage Small Cell Lung Cancer (ES-SCLC); Small Cell Lung Cancer (SCLC)

Treatments: Drug: carboplatin; Drug: obrixtamig; Drug: etoposide; Drug: atezolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT07472517

2025-520565-51-00 (Registry Identifier)

U1111-1317-4955 (Registry Identifier)

1438-0012

Details and patient eligibility

About

This study is open to adults with advanced small cell lung cancer (SCLC). The purpose of this study is to find out if a study medicine called obrixtamig plus standard treatment (atezolizumab, carboplatin, and etoposide) improves survival when compared to standard treatment alone. Obrixtamig is an antibody-like molecule that may help the immune system fight cancer. Another purpose of the study is to test a medical device being developed to measure levels of the tumour marker DLL3.

Participants are put into 2 groups randomly, which means by chance. One group receives obrixtamig and standard treatment. The other group receives standard treatment without obrixtamig. All treatments are given as infusions into a vein.

Participants are in the study for up to 3 years. During this time, they visit the study site regularly. Participants in the group receiving obrixtamig stay overnight at the study site following the first 2 obrixtamig treatments. At the visits, doctors check the size of the tumour(s). The results are compared between the 2 groups to see whether the treatment works. The doctors also regularly check participants' health and take note of any unwanted effects.

Enrollment: 670 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria :

1. Patients with histologically confirmed Extensive-stage Small Cell Lung Cancer (ES-SCLC)

2. Patients without any previous systematic anti-cancer treatment for ES-SCLC. Patients who received previous systematic anti-cancer treatment during limited stage are eligible if the treatment has been completed more than 6 months before the diagnosis of ES-SCLC.

3. Adequate archival formalin-fixed paraffin-embedded (FFPE) tumour tissue, as specified in the Laboratory Manual, must be available for central laboratory analysis of Delta-like ligand 3 (DLL3) expression status and other biomarkers. The central laboratory investigational VENTANA DLL3 (SP347) RxDx test result must be available prior to randomisation.

4. Patients with asymptomatic brain metastasis are eligible if they meet one of the following criteria:

   • Treatment for brain metastases (e.g. whole brain radiation therapy, stereotactic radiotherapy, or radiosurgery) completed at least 14 days prior to randomisation and neurologically stable without the use of glucocorticoids or therapeutic anti-convulsant for at least 7 days prior to randomisation
   • Untreated brain metastases that do not require treatment and are neurologically stable without the use of glucocorticoids or therapeutic anti-convulsant for at least 28 days prior to randomisation

5. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1

6. Eligible for continuing carboplatin + etoposide + atezolizumab regimen as first-line Standard of care (SoC) treatment within 28 days after the start of the initial cycle of standard therapy

7. Eligible to receive treatment with full dose of atezolizumab, carboplatin, and etoposide as first-line SoC treatment, in accordance with the approved Summary of Product Characteristics if provided centrally or approved local product label if provided by the trial site Further inclusion criteria apply.

Exclusion Criteria :

1. Presence of leptomeningeal disease and/or carcinomatous meningitis
2. Previous treatment targeting DLL3 (e.g. T cell engagers (TcEs), cell therapies, antibody-drug conjugates, or radiopharmaceuticals)
3. Radiotherapy of any anatomical sites within 14 days prior to randomisation
4. Persistent toxicity from previous treatments that has not resolved to ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (except for alopecia, asthenia/fatigue, amenorrhea/menstrual disorders, CTCAE Grade 2 peripheral neuropathy, and CTCAE Grade 2 endocrinopathies controlled by replacement therapy, and toxicities, which are considered irreversible but stable for at least 4 weeks prior to randomisation, per investigator judgment)
5. Patient with active autoimmune disease or a documented history of autoimmune disease that requires systemic treatment (e.g. glucocorticoids or immunosuppressive drugs). Patients with vitiligo, resolved childhood asthma/atopy, alopecia, or any chronic skin condition that does not require systemic therapy, patients with autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and/or controlled Type 1 diabetes mellitus on a stable insulin regimen may be included if in the opinion of the investigator it is appropriate and safe to do so.

Further exclusion criteria apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

670 participants in 2 patient groups

obrixtamig + atezolizumab, carboplatin, and etoposide treatment arm

Experimental group

Treatment:

Drug: atezolizumab

Drug: etoposide

Drug: carboplatin

Drug: obrixtamig

atezolizumab, carboplatin, and etoposide control arm

Experimental group

Treatment:

Drug: atezolizumab

Drug: etoposide

Drug: carboplatin