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 metastatic disease. Participants with mixed histology must be classified based on the main component. Participants with NSCLC are eligible with any or no PD-L1 expression. Participants with AGA-positive disease must have received targeted therapy prior to enrollment 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 the first-line/treatment-naïve cohorts in the advanced/metastatic setting. Prior treatment with ADC with topoisomerase inhibitor payload is only allowed for participants in the second-line plus cohorts in the advanced/metastatic setting.
* Is a candidate to locoregional treatment (including surgical resection, stereotactic radiotherapy or tumor ablation) with potential to induce complete or near complete response and prolonged tumor control (sometimes described as "radical" intent), per investigator's assessment.
* Has a history of significant hematologic toxicity to prior lines of therapy, as assessed by investigator, e.g., Grade 4 febrile neutropenia or recurrent/persistent Grade 3 to 4 neutropenia.

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

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 02/24/2026. Questions regarding updates should be directed to the study team contact.