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

This is a Phase II, multi-site, open-label, parallel group study in participants with untreated extended-stage small-cell lung cancer (ES-SCLC) (Cohort 1) or small-cell lung cancer (SCLC) which has progressed on first- or second-line treatment (Cohort 2 and Cohort 3). This study will assess the safety, efficacy, and pharmacokinetics (PK) of BNT327.

Inclusion Criteria (applicable to all participants unless otherwise specified): * Cohort 1 only: Have histologically or cytologically confirmed ES-SCLC (using the American Joint Committee on Cancer \[AJCC\]) tumor node metastasis \[TNM\] staging system combined with Veterans Administration Lung Study Group two-stage classification scheme). For AJCC TNM 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. * Cohort 1 only: Participants who have not received systemic therapy for ES-SCLC for various reasons including potential intolerance of the standard-of-care per the patient's treating physician's judgment. However, participants with prior chemoradiotherapy for Limited-Stage Small-Cell Lung Cancer (LS-SCLC) must have been treated with curative intent and had a treatment-free interval of at least 6 months since the last systemic anticancer treatment including chemotherapy, radiotherapy, or chemoradiotherapy before the diagnosis of ES-SCLC to be eligible. * Cohort 2 and Cohort 3 only: Participants with SCLC who have disease progression/relapse after first-line platinum-based chemotherapy with or without immunotherapy, or after first-line platinum-based chemotherapy and one second-line of chemotherapy (not the same chemotherapy agent in the specific arm to be enrolled to) with time to progression ≥3 months during second-line treatment. * Have given informed consent by signing and dating an informed consent form before initiation of any study-specific procedures. * Male or female, aged ≥18 years at the time of giving informed consent. * Are willing and able to comply with scheduled visits, treatment schedule, the planned study assessments, laboratory tests, lifestyle restrictions, and other requirements of the study. This includes that they are able to understand and follow study-related instructions. * Have at least one measurable lesion as the targeted lesion based on RECIST 1.1. 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 performance status of 0 or 1. * Have a minimum life expectancy of \>3 months. * Have adequate organ function, as defined below: * Hematology: * Absolute neutrophil count ≥1.5 × 10\^9/L. * Platelet count ≥100 × 10\^9/L. * Hemoglobin ≥90 g/L or 5.6 mmol/L. * Liver function: * Total bilirubin ≤1.5 × upper limit of normal (ULN). * With Gilbert's syndrome total bilirubin \480 ms (the electrocardiogram can be repeated at the discretion of the investigator). * Use of cardiac pacemaker. * Cardiac troponin I or T \>2 x ULN. * Have any of the following hypertension or diabetic conditions prior to initiation of study treatment: * Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg) while on antihypertensive medicine. * Those with a history of hypertensive crisis or hypertensive encephalopathy. * Poorly controlled diabetes (fasting blood glucose ≥13.3 mmol/L \[240 mg/dL\]). * Have serious non-healing wounds, ulcers, or bone fractures. This includes history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess for which an interval of 6 months must pass before enrollment into this study. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation. * Participants with 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 initiation of study treatment. * Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters (e.g., PleurX) are allowed. However, participants who are clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis or with indwelling catheters, e.g., PleurX) are allowed. * Participants with a history of serious Grade 3 or higher immune-related adverse events (irAEs) that led to treatment discontinuation of a prior immunotherapy. Participants with a history of Grade ≥3 irAEs that did not lead to discontinuation of a prior immunotherapy but fully recovered may be enrolled per investigator's discretion. The investigator may request sponsor guidance in such cases. * Have a known or suspected hypersensitivity to the study treatments including any active ingredient or excipients thereof. * Have known human immunodeficiency virus infection or known acquired immunodeficiency syndrome, with the following exceptions: * Participants with cluster of differentiation 4 (CD4)+ T-cell (CD4+) counts ≥350 cells/µL per local laboratory should generally be eligible for the study. * Participants who have not had an opportunistic infection within the past 12 months. * Have a known history/positive serology for hepatitis B requiring active antiviral therapy (unless immune due to vaccination or resolved natural infection or unless passive immunization due to immunoglobulin therapy). Individuals with positive serology must have hepatitis B virus viral load below the limit of quantification. * Have an active hepatitis C virus infection; individuals who have completed curative antiviral treatment with hepatitis C virus viral load below the limit of quantification are allowed. * Participants with AEs from prior antitumor therapy whose AE(s) have not returned to Grade 1 (graded by NCI CTCAE v5.0 criteria) or below (unless the investigator determines that certain AEs pose no safety risk to participants, such as hair loss, Grade 2 peripheral neuropathy or stable hypothyroidism under hormone replacement therapy) are not eligible for the study. * Have superior vena cava syndrome or symptoms of spinal cord compression. * Those with active, or a history of, pneumonitis requiring treatment with steroids, or has active, or a history of, interstitial lung disease. Those with a history of pulmonary fibrosis, or currently diagnosed with severe lung diseases such as interstitial pneumonia, pneumoconiosis, chemical pneumonitis, or any other condition resulting in significant impairment in lung function. Exception: Asymptomatic interstitial changes caused by previous radiation therapy, chemotherapy, or other factors such as smoking are acceptable. * Have active tuberculosis. * Have underlying condition(s) that may increase the risk of the combination treatment or complicate the interpretation of AEs, as judged by the investigator, or other scenarios in which the investigator consider the participant as not eligible for the study. * Are vulnerable individuals, i.e., are individuals whose willingness to volunteer in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. This includes all sponsor, study site, or third party (e.g., contract research organization, vendor) personnel directly involved in the conduct of the sudy and their family members or dependents, as well as all study site personnel otherwise supervised by the investigator.