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

This study will consist of 2 parts: dose optimization (Part 1) and extension (Part 2). In the dose optimization part of the study (Part 1), approximately 80 participants with at least 1 prior line of platinum-based chemotherapy and a maximum of 3 prior lines of therapy will be enrolled. Two I-DXd doses will be tested (8 mg/kg once every 3 weeks and 12 mg/kg once every 3 weeks). In the extension part of the study (Part 2), approximately 70 participants with a minimum of two previous lines of systemic therapy will be enrolled. I-DXd will be administered at the selected dose of 12 mg/kg once every 3 weeks (Q3W). In Part 1, eligible participants will be randomized in a 1:1 ratio to receive one of the two dose levels of I-DXd. Randomization will be stratified by: 1. Prior receipt or of an anti-programmed death-ligand 1 (PD-\[L\]1) antibody (yes/no) 2. The chemotherapy-free interval (CTFI) from completion of the first-line therapy to the date of documented radiological Progressive Disease of \<90 days vs. ≥90 days in second-line participants as well as the number of lines of therapy. Thus, the stratification factor includes three categories: (1) second-line participants with CTFI \<90 days, (2) second-line participants with CTFI ≥90 days, and (3) third- and fourth-line participants.