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

Inclusion Criteria:

• Have histologically or cytologically confirmed ES-SCLC (using the AJCC [AmericanJoint Committee on Cancer] tumor node metastasis staging system combined withVeterans Administration Lung Study Group [VALG]'s two stage classification scheme).

• For AJCC tumor node metastasis staging system: AJCC 8th edition stage IV (Tany, N any, M1a/b/c), or T3~4 for multiple lung nodules or tumor/nodule volumethat cannot be encompassed in a tolerable radiotherapy plan.

• Have not had prior systemic therapy for ES-SCLC. However, participants with priorchemoradiotherapy or immunotherapy for limited-stage-SCLC must have been treatedwith curative intent and had a treatment-free interval of at least 6 months afterthe 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, interventionalprocedures, etc.) are generally not considered as target lesions. If the lesion withprior local treatment is the only targeted lesion, evidence-based radiology must beprovided to demonstrate disease progression (the single bone metastasis or thesingle central nervous system metastasis should not be considered as a measurablelesion).

• 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 timeintervals prior to study treatment:

• Within 2 weeks: small molecule agents with half-life of <7 days; radiation notinvolving 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 moleculetargeted agents with half-life of ≥7 days; monoclonal antibodies, antibody-drugconjugates, 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 ofprednisone or an equivalent dose of other corticosteroids) within 10 days priorto the initiation of study treatment. Note: local, intranasal, intraocular,intra-articular or inhaled corticosteroids, short-term use (≤7 days) ofcorticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) ortreatment of non-autoimmune conditions (e.g., delayed hypersensitivityreactions 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 notneurologically stable or on steroids within 10 days before initiating studytreatment of this study.

• Participants with known leptomeningeal metastases.

• Have uncontrolled hypertension or poorly controlled diabetes prior to studytreatment.

• Have serious non-healing wound, ulcer, or bone fracture. This includes history ofabdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, orintra-abdominal abscess for which an interval of 6 months must pass before studyentry. In addition, the participant must have undergone correction (or spontaneoushealing) of the perforation/fistula and/or the underlying process causing thefistula/perforation.

• Have evidence of major coagulation disorders or other significant risks ofhemorrhage 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 priorto the study treatment.

• Have superior vena cava syndrome or symptoms of spinal cord compression.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.