Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC)

Inclusion Criteria:

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

• Sign and date the informed consent form (ICF) prior to the start of anystudy-specific qualification procedures.

• Participant must have at least one lesion, not previously irradiated, amenable tocore biopsy.

• Male or female subjects aged ≥18 years (follow local regulatory requirements if thelegal age of consent for study participation is >18 years old).

• Histologically or cytologically documented ES-SCLC.

• At least one measurable lesion according to RECIST v1.1 as assessed by theinvestigator.

• Prior therapy with at least one platinum-based line as systemic therapy forextensive-stage disease with at least two cycles of therapy (except in the case ofearly objective PD) and beginning with protocol version 3.0, a minimum of twoprevious lines of systemic therapy.

• Documentation of radiological disease progression on or after most recent systemictherapy.

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.

Exclusion Criteria:

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

• Prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents,including I-DXd.

• Prior discontinuation of an antibody drug conjugate (ADC) that consists of anexatecan derivative (eg, trastuzumab deruxtecan) due to treatment-relatedtoxicities.

• Clinically active brain metastases, spinal cord compression or leptomeningealcarcinomatosis, defined as untreated or symptomatic, or requiring therapy withsteroids or anticonvulsants to control associated symptoms.

• Any of the following conditions within the past 6 months: cerebrovascular accident,transient ischemic attack, or another arterial thromboembolic event.

• Clinically significant corneal disease.

• Uncontrolled or significant cardiovascular disease.

• History of (non-infectious) interstitial lung disease (ILD)/pneumonitis thatrequired corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis thatcannot be ruled out by imaging at screening.

• Clinically severe pulmonary compromise resulting from intercurrent pulmonaryillnesses,

• Chronic steroid treatment (dose of 10 mg daily or more prednisone equivalent),except for low-dose inhaled steroids (for asthma/COPD) or topical steroids (for mildskin conditions) or intra-articular steroid injections.

• History of malignancy other than SCLC within the 3 years prior to enrollment, exceptadequately resected non-melanoma skin cancer, curatively treated in situ disease,superficial gastrointestinal (GI) tract tumors and non-muscle invasive bladdercancer curatively resected by endoscopic surgery.

• History of allogeneic bone marrow, stem cell, or solid organ transplant.

• Unresolved toxicities from previous anticancer therapy, defined as toxicities (otherthan alopecia) not yet resolved to National Cancer Institute- Common TerminologyCriteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0), Grade ≤1 or baseline.

• History of hypersensitivity to the drug substances, inactive ingredients in the drugproduct or severe hypersensitivity reactions to other monoclonal antibodies.

• Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.

• Has active or uncontrolled hepatitis B or C infection.

• Active, known, or suspected autoimmune disease.

• Any evidence of severe or uncontrolled systemic diseases (including active bleedingdiatheses, psychiatric illness/social situations, substance abuse).

• Has received a live vaccine within 30 days prior to the first dose of study drug.

• Female who is pregnant or breast-feeding or intends to become pregnant during thestudy.

• Prior or ongoing clinically relevant illness, medical condition, surgical history,physical finding, or laboratory abnormality that, in the investigator's opinion,could affect the safety of the participant.

• Known human immunodeficiency virus (HIV) infection that is not well controlled.