safety and effectiveness of bnt327, an investigational therapy in combination with chemotherapy for patients with untreated small-cell lung cancer

Conditions: Extensive-stage Small-cell Lung Cancer

Summary: this is a phase iii, multisite, randomized, double-blinded study to investigate bnt327 combined with chemotherapy (etoposide/carboplatin) compared to atezolizumab combined with chemotherapy (etoposide/carboplatin) for the treatment of participants with previously untreated extensive-stage small-cell lung cancer (es-sclc).

the study consists of a screening period (up to 21 days), an induction period followed by a maintenance period (until confirmed disease progression, intolerable toxicity, participant withdrawal, study termination or up to 2 years \[whichever occurs first\]), and a follow-up (fu) period for all participants (2 safety fu visits and survival fu visits). eligible patients will be randomized (1:1:1) to the treatment arms (arm 1, arm 2, and arm 3), until one arm stops accrual. participants will then be randomized (1:1) in the remaining two treatment arms (arm 1 and arm 2 or arm 3). the randomization will be stratified based on the following factors: 1. brain metastases per investigator assessment; 2. liver metastases per investigator assessment; and 3. geography.

Eligibility criteria:
inclusion criteria: * have histologically or cytologically confirmed es-sclc (using the ajcc \[american joint committee on cancer\] tumor node metastasis staging system combined with veterans administration lung study group \[valg\]'s two stage classification scheme). * for ajcc tumor node metastasis staging system: ajcc 8th edition stage iv (t any, n any, m1a/b/c), or t3\~4 for multiple lung nodules or tumor/nodule volume that cannot be encompassed in a tolerable radiotherapy plan. * have not had prior systemic therapy for es-sclc. however, participants with prior chemoradiotherapy or immunotherapy for limited-stage-sclc must have been treated with curative intent and had a treatment-free interval of at least 6 months after the last systemic anticancer treatment including chemotherapy, radiotherapy, immunotherapy, or chemoradiotherapy before diagnosis of es-sclc to be eligible. * have at least one measurable lesion as the targeted lesion based on recist v1.1. lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures, etc.) are generally not considered as target lesions. if the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system metastasis should not be considered as a measurable lesion). * eastern cooperative oncology group (ecog) performance status of 0 or 1. * adequate hematologic and organ function. exclusion criteria: * have histologically or cytologically confirmed sclc with combined histologies. * have received any of the following therapies or drugs within the noted time intervals prior to study treatment: * within 2 weeks: small molecule agents with half-life of \<7 days; radiation not involving the thoracic cavity; local radiation for brain lesions is allowed; local radiation for bone lesions is allowed. * within 4 weeks: radiation involving the thoracic cavity; small molecule targeted agents with half-life of ≥7 days; monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or t-cell or other cell-based therapies. * have received prior treatment with a programmed death (ligand)-1 (pd\[l\]-1)/vascular endothelial growth factor (vegf) bispecific antibody. * have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 10 days prior to the initiation of study treatment. note: local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short-term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens) are allowed. * have the following central nervous system metastases: * participants with untreated brain metastases that are symptomatic or large (e.g., greater than 2 cm). * participants with treated central nervous system (cns) metastases who are not neurologically stable or on steroids within 10 days before initiating study treatment of this study. * participants with known leptomeningeal metastases. * have uncontrolled hypertension or poorly controlled diabetes prior to study treatment. * have serious non-healing wound, ulcer, or bone fracture. this includes history of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess for which an interval of 6 months must pass before study entry. in addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation. * have evidence of major coagulation disorders or other significant risks of hemorrhage such as: * history of intracranial or intraspinal hemorrhage. * tumor lesions invading large vessels and with significant risk of bleeding. * had clinically significant hemoptysis or tumor hemorrhage within 1 month prior to the study treatment. * have superior vena cava syndrome or symptoms of spinal cord compression. note: other protocol defined inclusion/exclusion criteria may apply.

Keywords: first-line es-sclc sclc immunotherapy in combination with chemotherapy untreated bispecific antibody programmed death-ligand 1 (pd-l1) vascular endothelial growth factor (vegf) a immunotherapy combination with other investigational agents