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

Phase 1/2, Multicenter, Open-label, Multiple-Dose First-in-human Study of U3-1402, in Subjects With HER3 Positive Metastatic Breast Cancer

This is an open-label, three-part, multiple-dose study to evaluate safety, tolerability, and efficacy of U3-1402 in patients with HER3-positive metastatic breast cancer. HER3 is a unique member of the human epidermal growth factor receptor, which defines a certain type of cancer.

The number of patients and treatment cycles are not fixed in this study. Subjects who continue to derive clinical benefit from the study treatment in the absence of withdrawal of consent, progressive disease (PD), unacceptable toxicity, or death may continue the study treatment until the end of the trial.

Key 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. (With exception of Dose Expansion Part TNBC cohort. See additional inclusion criteria for Dose Expansion Part TNBC cohort.)

   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 hormone (estrogen and/or progesterone) receptor (HR)-positive and HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines. (With exception of Dose Expansion Part TNBC cohort. See additional inclusion criteria for Dose Expansion Part TNBC cohort.)

    Additional Inclusion Criteria for Dose Expansion Part TNBC cohort Only:

11. Has documented hormone (estrogen and progesterone) receptor (HR)-negative and HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines

12. Has progressed after receiving 1 to 2 prior chemotherapy regimens for advanced/unresectable or metastatic breast cancer.

Key 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 radiation pneumonitis) or who are suspected to have these diseases by imaging at screening period

7. Has clinically significant corneal disease

   Additional Exclusion Criteria for Dose Expansion Part:

8. Prior treatment with an govitecan derivative (eg, IMMU-132).