Safety and Efficacy 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 (T any, Nany, M1a/b/c), or T3~4 for multiple lung nodules or tumor/nodule volume that cannotbe encompassed in a tolerable radiotherapy plan.

• Have not had prior systemic therapy for ES-SCLC. However, participants with priorchemoradiotherapy for limited-stage-SCLC must have been treated with curative intentand had a treatment-free interval of at least 6 months after the last chemotherapy,radiotherapy, 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 as defined in the protocol.

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; radiationoutside the thoracic cavity including whole brain radiation. Of note, otherlocal radiation for brain lesions (not whole brain) is allowed; local radiationfor bone lesions is allowed. Palliative bone radiation or brain stereotacticradiosurgery would not require a washout period, but participants shouldrecover from radiotherapy-related toxicity.

• 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 anti-vascular endothelial growth factor (VEGF) monoclonal antibody, or programmed death (ligand)-1 (PD[L]-1)/VEGFbispecific antibody.

• Have received systemic corticosteroids (at a dosage greater than 10 mg/day ofprednisone or an equivalent dose of other corticosteroids) within 7 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 (at a dosage greater than 10 mg/Day ofprednisone or an equivalent dose of other corticosteroid) within 7 days beforeinitiating study treatment of this study.

• Participants with known leptomeningeal metastases.

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

• Have a serious or non-healing wound, or (incompletely healed) bone fracture. Thisincludes history of abdominal fistula, tracheoesophageal fistula, gastrointestinalperforation, or intra-abdominal abscess for which an interval of 6 months must passbefore study entry. In addition, the participant must have undergone correction (orspontaneous healing) of the perforation/fistula and/or the underlying processcausing the fistula/perforation.

• Have a significant risk of hemorrhage (per investigator clinical judgment) asdefined in the protocol.

• Have superior vena cava syndrome or symptoms of spinal cord compression thatrequires urgent medical intervention.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.