A Clinical Study to Investigate the Efficacy and Safety of an Investigational Combination Therapy With BNT324 and BNT327 in Patients With Advanced Lung Cancer

Inclusion Criteria:

• Aged ≥18 years at the time of giving informed consent.

• Histological or cytological confirmed unresectable advanced/metastatic lung cancer.Histological classification may be based on tumor samples prior to metastaticdisease. Participants with mixed histology must be classified based on the maincomponent. Participants with NSCLC are eligible with any or no PD-L1 expression.Participants with AGA-positive disease must have received targeted therapy prior toenrollment in this study.

• Part 1: Participants with NSCLC and SCLC

• Part 2 Cohort 1: Participants with NSCLC (subpopulation 1) AGA negative, 1L

• Part 2 Cohort 2: Participants with SCLC, 2L+

• Part 2 Cohort 3: Participants with NSCLC (subpopulation 1) AGA negative, 2L+

• Part 2 Cohort 4: Participants with NSCLC (subpopulation 2) AGA negative, 1L

• Part 2 Cohort 5: Participants with NSCLC (subpopulation 2) AGA negative, 2L+

• Part 2 Cohort 6: Participants with NSCLC AGA positive

• Part 2 Cohort 7: Participants with SCLC, 1L

• Have measurable disease defined by RECIST version 1.1.

• Have an Eastern Cooperative Oncology Group performance status of 0 or 1.

• Have a life expectancy of ≥12 weeks.

Exclusion Criteria:

• Prior treatment with B7-H3 targeted therapy.

• Prior treatment with ADC with topoisomerase inhibitor (e.g., datopotamab deruxtecan,trastuzumab deruxtecan). Note: This exclusion applies to participants in thefirst-line/treatment-naïve cohorts in the advanced/metastatic setting. Priortreatment with ADC with topoisomerase inhibitor payload is only allowed forparticipants in the second-line plus cohorts in the advanced/metastatic setting.

• Is a candidate to locoregional treatment (including surgical resection, stereotacticradiotherapy or tumor ablation) with potential to induce complete or near completeresponse and prolonged tumor control (sometimes described as "radical" intent), perinvestigator's assessment.

• Has a history of significant hematologic toxicity to prior lines of therapy, asassessed by investigator, e.g., Grade 4 febrile neutropenia or recurrent/persistentGrade 3 to 4 neutropenia.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply to all or some participants depending on the cohort.