Phase I/II Study of U3-1402 in Subjects With Human Epidermal Growth Factor Receptor 3 (HER3) Positive Metastatic Breast Cancer

Inclusion Criteria:

1. Is 18 Years and older in the United States or 20 Years and older in Japan

2. Has a pathologically documented advanced/unresectable or metastatic breast cancer

3. Documented HER3-positive disease measured by immunohistochemistry (IHC)

4. Has disease that is refractory to or intolerable with standard treatment, or for which
standard treatment no longer is available

5. Has an Eastern Cooperative Oncology Group Performance Status 0-1

6. Has Left Ventricular Ejection Fraction ≥ 50%

7. Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)
version 1.1

Additional Inclusion Criteria for Dose Finding Part and Dose Expansion Part:

8. Has received 2-6 prior chemotherapy regimens for breast cancer, at least 2 of which
were administered for treatment of advanced/unresectable or metastatic disease. At
least 1 prior chemotherapeutic regimen must have included a taxane, administered in
the neoadjuvant, adjuvant, or advanced setting.

Additional Inclusion Criteria for Dose Expansion Part Only:

9. Is able to submit a fresh tumor biopsy sample prior to starting study treatment if not
already submitted for HER3 expression

10. Has documented HER2 negative expression according to American Society of Clinical
Oncology - College of American Pathologists (ASCO-CAP) guidelines

11. Has documented hormone (estrogen and/or progesterone) receptor (HR)-positive disease

Exclusion Criteria:

1. Prior treatment with a HER3 antibody

2. Prior treatment with an antibody-drug conjugate (ADC) which consists of an exatecan
derivative that is a topoisomerase I inhibitor (eg, DS-8201)

3. Has a medical history of symptomatic congestive heart failure (New York Heart
Association classes II-IV) or serious cardiac arrhythmia requiring treatment

4. Has a medical history of myocardial infarction or unstable angina

5. Has a corrected QT prolongation to > 450 millisecond (ms) in males and > 470 ms in
females

6. Has a medical history of clinically significant lung diseases (eg, interstitial
pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or who
are suspected to have these diseases by imaging at screening period

7. Has clinically significant corneal disease