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

Official title

DAREON ® -Lung-1: A Phase III Multi-center, Open-label, Randomised Trial of Intravenous Obrixtamig in Combination With Atezolizumab, Carboplatin, and Etoposide vs. Atezolizumab, Carboplatin, and Etoposide as First-line Treatment in Patients With Extensive-stage Small Cell Lung Cancer

Overview

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.

Interventions

• Drug obrixtamig
  obrixtamig
• Drug atezolizumab
  atezolizumab
• Drug carboplatin
  carboplatin
• Drug etoposide
  etoposide

Primary outcome measures

• Overall survival (OS) [Time frame: Up to 36 months]

Secondary outcome measures (10)

• Progression free survival (PFS) [Time frame: Up to 36 months]
• Change From Baseline in Selected Disease Symptoms Included in the European Organization for Research and Treatment of Lung Cancer Quality of Life Questionnaire (EORTC-QLQ-LC13) [Time frame: At baseline and up to 1 year]
• Overall response (OR) [Time frame: Up to 36 months]
• Occurrence of treatment-emergent Cytokine Release Syndrome (CRS) during the on-treatment period [Time frame: Up to 36 months]
• Occurrence of treatment-emergent Immune effector cell-associated neurotoxicity syndrome (ICANS) during the on-treatment period [Time frame: Up to 36 months]
• Occurrence of treatment-emergent adverse events (AEs) leading to trial medication discontinuation during the on-treatment period [Time frame: Up to 36 months]
• Occurrence of treatment-emergent AEs leading to trial medication dose delay during the on-treatment period [Time frame: Up to 36 months]
• Occurrence of treatment-emergent AEs leading to trial medication dose reduction during the on-treatment period [Time frame: Up to 36 months]
• 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 [Time frame: Up to 3 weeks]
• Change From Baseline in Symptom Severity as Measured by scales of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-LC13 [Time frame: At baseline and up to 1 year]

Eligibility criteria

Inclusion criteria

• Patients with histologically confirmed Extensive-stage Small Cell Lung Cancer (ES-SCLC)
• 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.
• 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.
• 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
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
• 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
• 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

• Presence of leptomeningeal disease and/or carcinomatous meningitis
• Previous treatment targeting DLL3 (e.g. T cell engagers (TcEs), cell therapies, antibody-drug conjugates, or radiopharmaceuticals)
• Radiotherapy of any anatomical sites within 14 days prior to randomisation
• 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)
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 33 centers

• Beijing Cancer Hospital — Beijing
• Beijing Chest Hospital, Capital Medical University — Beijing
• The First Affiliated Hospital Of Bengbu Medical College — Bengbu
• Hunan Province Tumor Hospital — Changsha
• Sichuan Cancer Hospital — Chengdu
• West China Hospital, Sichuan University — Chengdu
• Fujian Cancer Hospital — Fuzhou
• Sun Yat-Sen University Cancer Center — Guangzhou
• … and 25 more centers

United States · 17 centers

• Infirmary Cancer Care — Mobile
• University of Arkansas for Medical Sciences — Little Rock
• Bioresearch Partner - Hialeah Hospital — Hialeah
• Emory University — Atlanta
• Norton Cancer Institute, Downtown — Louisville
• Pikeville Medical Center — Pikeville
• Epic Medical Research - Monroe — Monroe
• Ochsner Medical Center — New Orleans
• … and 9 more centers

Spain · 17 centers

Center list to be confirmed — check the primary protocol.

Germany · 14 centers

Center list to be confirmed — check the primary protocol.

Japan · 12 centers

Center list to be confirmed — check the primary protocol.

France · 10 centers

Center list to be confirmed — check the primary protocol.

Italy · 10 centers

Center list to be confirmed — check the primary protocol.

South Korea · 10 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 10 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 7 centers

Center list to be confirmed — check the primary protocol.

Hungary · 6 centers

Center list to be confirmed — check the primary protocol.

Mexico · 6 centers

Center list to be confirmed — check the primary protocol.

Argentina · 5 centers

• Hospital Britanico de Buenos Aires — CABA
• Clinica Adventista Belgrano — CABA
• Clinica Privada Independencia — Munro
• Sanatorio Allende S.A. — Nueva Córdoba
• Sanatorio Parque S.A. — Rosario

Chile · 5 centers

• Icegclinic — La Florida
• Clinica Santa Maria — Providencia
• Instituto Oncológico FALP — Providencia
• Bradford Hill- Centro de Investigación Clínica — Recoleta
• Clínica Alemana de Santiago S.A. — Santiago

Malaysia · 5 centers

Center list to be confirmed — check the primary protocol.

Portugal · 5 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 5 centers

Center list to be confirmed — check the primary protocol.

Brazil · 4 centers

• Hospital de Amor — Barretos
• Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa Sociedade Simples — Porto Alegre
• Irmandade da Santa Casa de Misericórdia de Porto Alegre — Porto Alegre - RS
• Fundação Faculdade Regional de Medicina de São José do Rio Preto — São José do Rio Preto

Poland · 4 centers

Center list to be confirmed — check the primary protocol.

Thailand · 4 centers

Center list to be confirmed — check the primary protocol.

Vietnam · 4 centers

Center list to be confirmed — check the primary protocol.

Australia · 3 centers

• Prince of Wales Hospital-Randwick-66496 — Randwick
• Cancer Research South Australia — Adelaide
• Ballarat Regional Integrated Cancer Centre — Ballarat

Austria · 3 centers

• Hospital Elisabethinen Linz — Linz
• Johannes Kepler University Linz — Linz
• Standort Penzing der Klinik Ottakring — Vienna

Belgium · 3 centers

• Universitair Ziekenhuis Antwerpen — Edegem
• Universitair Ziekenhuis Brussel — Jette
• UZ Leuven — Leuven

Bulgaria · 3 centers

• Multiprofile Hospital For Active Treatment-Uni Hospital Ltd. — Panagyurishte
• MHAT Heart and brain — Pleven
• Acibadem City Clinic Tokuda University Hospital EAD — Sofia

Finland · 3 centers

Center list to be confirmed — check the primary protocol.

Greece · 3 centers

Center list to be confirmed — check the primary protocol.

Netherlands · 3 centers

Center list to be confirmed — check the primary protocol.

Norway · 3 centers

Center list to be confirmed — check the primary protocol.

Romania · 3 centers

Center list to be confirmed — check the primary protocol.

Sweden · 3 centers

Center list to be confirmed — check the primary protocol.

Canada · 2 centers

• Verspeeten Family Cancer Centre (LHSC) — London
• Sault Area Hospital — Sault Ste. Marie

Czechia · 2 centers

• University Hospital Olomouc — Olomouc
• University Thomayer´s Hospital — Prague

Estonia · 2 centers

Center list to be confirmed — check the primary protocol.

Hong Kong · 2 centers

Center list to be confirmed — check the primary protocol.

Latvia · 2 centers

Center list to be confirmed — check the primary protocol.

New Zealand · 2 centers

Center list to be confirmed — check the primary protocol.

Singapore · 2 centers

Center list to be confirmed — check the primary protocol.

Switzerland · 2 centers

Center list to be confirmed — check the primary protocol.

Georgia · 1 center

Center list to be confirmed — check the primary protocol.

Ireland · 1 center

Center list to be confirmed — check the primary protocol.

Moldova · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07472517 · 1438-0012 · 2025-520565-51-00 · U1111-1317-4955

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗