Phase I/II, Two-Part, Multicenter First-in-Human Study of DS-7300a in Subjects with Advanced Solid Malignant Tumors

This study is in one single group of participants with advanced solid tumors who have not
been cured by other treatments. It is the first time the drug will be used in humans, and
will be in two parts.

The primary purpose of the parts are:

- Dose Escalation Part: To evaluate the safety and tolerability and to determine the
maximum tolerated dose and the recommended dose for expansion of ifinatamab deruxtecan
(I-DXd).

- Dose Expansion Part: To investigate the safety, tolerability and antitumor activity of
I-DXd when administered as a single agent.

This study is expected to last approximately 5 years from the time the first participant is
enrolled to the time the last participant is off the study.

The number of treatment cycles is not fixed in this study. Participants who continue to
benefit from the study treatment may continue, unless:

- they withdraw

- their disease gets worse

- they experience unacceptable side effects.

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 Solid
Tumors (RECIST) Version 1.1. Castrate-resistant prostate cancer (CRPC) participants
with bone only disease may be eligible on a case-by- case basis after discussion with
the Medical Monitor.

- 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 neck
squamous cell carcinoma, esophageal squamous cell carcinoma, squamous and
adenocarcinoma non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC),
bladder cancer, sarcoma, endometrial cancer, melanoma, adenocarcinoma CRPC (primary
neuroendocrine or histologically confirmed neuroendocrine differentiated prostate
cancer is not allowed), breast cancer that is refractory to or intolerable with
standard treatment, or for which no standard treatment is available.

Exclusion Criteria:

- Has prior treatment with B7-H3 targeted agent.

- Has prior treatment with an antibody drug conjugate that consists of an exatecan
derivative that is a topoisomerase I inhibitor (e.g., trastuzumab deruxtecan).

- Has multiple primary malignancies within 3 years, except adequately resected
non-melanoma skin cancer, curatively treated in situ disease, superficial GI tract
tumors and non-muscle invasive bladder cancer curatively resected by endoscopic
surgery.

- Uncontrolled significant cardiovascular disease

- Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
including, but not limited to, any underlying pulmonary disorder, or any autoimmune,
connective tissue or inflammatory disorders with potential pulmonary involvement,
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 safety
risk to the subject or interfere with participation of the subject or evaluation of
the clinical study in the opinion of the Investigator.