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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH, Boehringer Ingelheim Espana S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-05-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2025-520565-51-00

WHO UTN

U1111-1317-4955

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective is to demonstrate the superiority in overall survival (OS) in at least 1 of 2 populations: 1) the overall population and 2) the DLL3 high (≥50% TC) population.

Secondary objectives 5

1. Key secondary objectives: Demonstrate superiority in progression-free survival (PFS) and the change from baseline at Week 19 in the dyspnea symptom scale of EORTC QLQ-LC13 in at least 1 of 2 populations: 1) the overall population and 2) the DLL3 high (≥50% TC) population.
2. Evaluate whether obrixtamig in combination with atezolizumab, carboplatin, and etoposide vs. atezolizumab, carboplatin, and etoposide in at least 1 of 2 populations (the overall population and the population with the pre-defined DLL3 high [≥50% TC] status) improves objective response (OR) by estimating the odds ratio for the proportion of participants with OR.
3. Improves time to deterioration (TTD) of dyspnea, cough, and chest pain scales using EORTC QLQ-C30 and QLQ-LC13.
4. Improves the change from baseline at Week 19 in the EORTC QLQ-LC13 chest pain and cough symptom scales.
5. Assess the safety of these treatment combinations in both populations by descriptively assessing the proportion of participants with occurrences of treatment-emergent CRS, ICANS, treatment-emergent AEs leading to trial medication discontinuation, dose delay, and dose reduction during the on-treatment period.

Conditions and MedDRA coding

small cell lung cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Researchers can request access to the documents regarding this study using the link https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing, and upon a signed “Document Sharing Agreement”. Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined on the website. Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program. Access Criteria: For study documents – upon signing of a ‚Document Sharing Agreement‘. For study data – 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Patients with histologically confirmed ES-SCLC who have completed 1 cycle of first-line treatment (platinum, etoposide, with or without anti-PD-1/anti-PD-L1 therapy, administered at a minimum dose of cisplatin 75 mg/m2 or carboplatin AUC 5 and etoposide 80 mg/m2).
2. 2. Patients without any previous systematic anti-cancer treatment for ES-SCLC (except for the completed 1 cycle of first-line treatment). 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. 3. Adequate archival formalin-fixed paraffin-embedded (FFPE) tumour tissue, as specified in the Laboratory Manual, must be available for central laboratory analysis of DLL3 expression status and other biomarkers. The central laboratory investigational VENTANA DLL3 (SP347) RxDx test result must be available prior to randomisation.
4. 4. Patients with asymptomatic brain metastasis are eligible if they meet one of the following criteria: o 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 o 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. 5. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
6. 6. Eligible for continuing carboplatin + etoposide + atezolizumab regimen as first-line SoC treatment within 28 days after the start of the initial cycle of standard therapy.
7. 7. Eligible to receive treatment with full dose of atezolizumab (1200 mg fixed dose), carboplatin (AUC 5), and etoposide (80-100 mg/m2) 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.
8. Further inclusion criteria apply.

Exclusion criteria 6

1. 1. Presence of leptomeningeal disease and/or carcinomatous meningitis.
2. 2. Previous treatment targeting DLL3 (e.g. TcEs, cell therapies, antibody-drug conjugates, or radiopharmaceuticals).
3. 3. Radiotherapy of any anatomical sites within 14 days prior to randomisation.
4. 4. Persistent toxicity from previous treatments that has not resolved to ≤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. 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.
6. Further exclusion criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival.

Secondary endpoints 10

1. PFS, defined as the time from randomisation until the earliest date of tumour progression according to the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 based on investigator assessments or death from any cause.
2. Change from baseline to Week 19 in the dyspnea symptom subscale of the EORTC QLQ-LC13.
3. OR, defined as a best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 (based on investigator assessments) from the date of randomisation until the earliest date of disease progression, death, last evaluable tumour assessment before start of subsequent anti-cancer therapy, lost to follow-up, or withdrawal of consent.
4. Occurrence of treatment-emergent CRS during the on-treatment period.
5. Occurrence of treatment-emergent ICANS during the on-treatment period.
6. Occurrence of treatment-emergent AEs leading to trial medication discontinuation during the on-treatment period.
7. Occurrence of treatment-emergent AEs leading to trial medication dose delay during the on-treatment period.
8. Occurrence of treatment-emergent AEs leading to trial medication dose reduction during the on-treatment period.
9. Time to deterioration (TTD), defined as time from randomisation to deterioration maintained for 2 consecutive assessments or 1 assessment followed by death from any cause within 3 weeks for symptom scales: o Dyspnea as measured by EORTC-QLQ-C30 and EORTC-QLQ-LC13 o Chest pain as measured by EORTC-QLQ-LC13 o Cough as measured by EORTC-QLQ-LC13
10. Change from baseline to Week 19 in symptom scales of the and EORTC QLQ-LC13 o Chest pain as measured by EORTC-QLQ-LC13 o Cough as measured by EORTC-QLQ-LC13

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Boehringer Ingelheim International GmbH

Sponsor organisation

Boehringer Ingelheim International GmbH

Address

Binger Strasse 173

City

Ingelheim Am Rhein

Postcode

55216

Country

Germany

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Third parties 2

Boehringer Ingelheim Espana S.A.

Sponsor organisation

Boehringer Ingelheim Espana S.A.

Address

Carrer Prat De La Riba 50, Sant Cugat Del Valles Sant Cugat Del Valles

City

Barcelona

Postcode

08174

Country

Spain

Sponsor responsibilities

Article 77 compliance

Boehringer Ingelheim International GmbH

Contact point sponsor

Boehringer Ingelheim International GmbH

Article 77 implementation

Boehringer Ingelheim International GmbH

Locations

20 EU/EEA countries · 101 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 378 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications