A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer

Participants must meet all the following criteria to be eligible for randomization into the study:

• Sign and date the informed consent form prior to the start of any study-specific qualification procedures.
• Adults ≥18 years or the minimum legal adult age (whichever is greater) at the time the informed consent form is signed.
• Has histologically or cytologically documented extensive-stage small cell lung cancer (ES-SCLC).
• The participant must provide adequate baseline tumor samples with sufficient quantity and quality of tumor tissue content.
• Has received prior therapy with only one prior platinum-based line as systemic therapy for SCLC with at least 2 cycles of therapy and a chemotherapy free-interval of ≥30 days.
• Has at least 1 measurable lesion according to RECIST v1.1 as assessed by the investigator.
• Has documentation of radiological disease progression on or after the most recent systemic therapy.
• Has ECOG PS of ≤1 within 7 days prior to Cycle 1 Day 1 (C1D1).
• Has no evidence of brain or leptomeningeal disease (spinal cord or central nervous system [CNS] metastases) based on history and physical examination. Subjects must require no treatment with steroids or anticonvulsants and have a stable neurologic status for at least 2 weeks prior to the first dose of study drug.

Participants who meet any of the following criteria will be disqualified from entering the study:

• Has received prior treatment with orlotamab, enoblituzumab, or other B7 homologue 3 (B7-H3) targeted agents, including I-DXd.
• Prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities.
• Has received any of the comparators used in this study or any topoisomerase I inhibitor.
• Has inadequate washout period before randomization as specified in the protocol.
• Has any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
• Has uncontrolled or significant cardiovascular disease.
• Has clinically significant corneal disease.
• Has history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening.
• Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder and potential pulmonary involvement caused by any autoimmune, connective tissue, or inflammatory disorders, prior pneumonectomy, or requirement for supplemental oxygen.