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

Main inclusion criteria:
– 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
– Patients without any previous systemic anti-cancer treatment for ES-SCLC (except for the completed 1 cycle of first-line treatment). Patients who received previous systemic 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 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:
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
– Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
– 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
– 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

Main exclusion criteria:
– Presence of leptomeningeal disease and/or carcinomatous meningitis
– Previous treatment targeting DLL3 (e.g. 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 ≤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)