Study of Ifinatamab Deruxtecan (DS-7300a, I-DXd) in Participants With Advanced Solid Malignant Tumors

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

• Has at least 1 measurable lesion according to Response Evaluation Criteria in SolidTumors (RECIST) Version 1.1 on computed tomography (CT) or magnetic resonanceimaging (MRI) as assessed by Investigator. Measurable lesions should not be from apreviously irradiated site. If the lesion at a previously irradiated site is theonly selectable target lesion, a radiological assessment showing significantprogression of the irradiated lesion should be provided by the Investigator

• Has adequate cardiac, hematopoietic, renal and hepatic functions

• Has an adequate treatment washout period prior to start of study treatment

• Has a pathologically documented advanced/unresectable or metastatic head and necksquamous cell carcinoma, esophageal squamous cell carcinoma, squamous andadenocarcinoma non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC),bladder cancer, sarcoma, endometrial cancer, melanoma, adenocarcinoma CRPC (primaryneuroendocrine or histologically confirmed neuroendocrine differentiated prostatecancer is not allowed), breast cancer that is refractory to or intolerable withstandard treatment, or for which no standard treatment is available.

For Expansion Cohort 4 2L ESCC participants only:

• Has disease progression a post platinum-based and an immune checkpoint inhibitor (ICI) treatment per global or local guidelines, with a maximum of one prior line ofsystemic therapy for unresectable advanced or metastatic ESCC.

Exclusion Criteria:

• Has prior treatment with B7-H3 targeted agent, including I-DXd.

• Has had prior discontinuation of an antibody drug conjugate (ADC) that consists ofan exatecan derivative (e.g., trastuzumab deruxtecan) due to treatment-relatedtoxicities.

• Has multiple primary malignancies within 3 years, except adequately resectednon-melanoma skin cancer, curatively treated in situ disease, superficial GI tracttumors and non-muscle invasive bladder cancer curatively resected by endoscopicsurgery.

• Uncontrolled significant cardiovascular disease

• Clinically severe pulmonary compromise resulting from intercurrent pulmonaryillnesses including, but not limited to, any underlying pulmonary disorder, or anyautoimmune, connective tissue or inflammatory disorders with potential pulmonaryinvolvement, prior pneumonectomy, or requirement for supplemental oxygen

• Has an uncontrolled infection requiring systemic therapy.

• Has substance abuse or any other medical conditions that would increase the safetyrisk to the subject or interfere with participation of the subject or evaluation ofthe clinical study in the opinion of the Investigator.