Small Cell Lung Cancer (SCLC), Extensive-stage Small Cell Lung Cancer (ES-SCLC)
Conditions
Brief summary
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
DRUGobrixtamig
obrixtamig
DRUGatezolizumab
atezolizumab
DRUGcarboplatin
carboplatin
DRUGetoposide
etoposide
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Up to 36 months | OS, defined as the time from randomisation until death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | Up to 36 months | 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 |
| 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) | At baseline and up to 1 year | EORTC QLQ-LC13: European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire lung cancer-specific 13-item questionnaire module (QLQ-LC13) includes one multi-item scale (dyspnoea, based on three items) and ten single-item measures capturing symptoms such as coughing, haemoptysis, pain, and treatment-related toxicities including sore mouth, dysphagia, and peripheral neuropathy. All QLQ-LC13 items are scored on a 4-point Likert scale (1 = "not at all," 4 = "very much"). All QLQ-LC13 scores range from 0 to 100, with higher scores indicating greater symptom burden or more severe problems |
| Overall response (OR) | Up to 36 months | OR, defined as a best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumours (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 |
| Occurrence of treatment-emergent Cytokine Release Syndrome (CRS) during the on-treatment period | Up to 36 months | — |
| Occurrence of treatment-emergent Immune effector cell-associated neurotoxicity syndrome (ICANS) during the on-treatment period | Up to 36 months | — |
| Occurrence of treatment-emergent adverse events (AEs) leading to trial medication discontinuation during the on-treatment period | Up to 36 months | — |
| Occurrence of treatment-emergent AEs leading to trial medication dose delay during the on-treatment period | Up to 36 months | — |
| Occurrence of treatment-emergent AEs leading to trial medication dose reduction during the on-treatment period | 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 | Up to 3 weeks | Assessments are a composite of the following European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ EORTC) scores: * Dyspnea as measured by EORTC-QLQ-C30 and EORTC-QLQ-LC13 * Chest pain as measured by EORTC-QLQ-LC13 * Cough as measured by EORTC-QLQ-LC13 These questionnaires request scores on global health status, functioning, symptoms, as well as single items to assess dyspnoea, insomnia, appetite loss, constipation, diarrhoea and financial difficulties. All scores range from 0 to 100. For scores regarding functioning and global quality of life, higher scores represent better functioning and better quality of life. For scores regarding symptom scales higher scores indicate greater symptom burden. |
| Change From Baseline in Symptom Severity as Measured by scales of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-LC13 | At baseline and up to 1 year | EORTC QLQ-LC13: EORTC Quality of Life Questionnaire lung cancer-specific 13-item questionnaire module (QLQ-LC13) includes one multi-item scale (dyspnoea, based on three items) and ten single-item measures capturing symptoms such as coughing, haemoptysis, pain, and treatment-related toxicities including sore mouth, dysphagia, and peripheral neuropathy. All QLQ-LC13 items are scored on a 4-point Likert scale (1 = "not at all," 4 = "very much"). All QLQ-LC13 scores range from 0 to 100, with higher scores indicating greater symptom burden or more severe problems |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, Estonia, Finland, France, Georgia, Germany, Greece, Hong Kong, Hungary, Ireland, Italy, Japan, Latvia, Malaysia, Mexico, Moldova, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Contacts
CONTACTBoehringer Ingelheim
Outcome results
None listed