Safety and Effectiveness of BNT327, an Investigational Therapy in Combination With Chemotherapy for Patients With Untreated Small-cell Lung Cancer

Eligibility 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.
• * 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 trial 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 trial 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 IMP of this trial.
• * Participants with known leptomeningeal metastases.
• * 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 trial 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 trial treatment.
• * Have superior vena cava syndrome or symptoms of spinal cord compression.