A Study of U3-1402 (Patritumab Deruxtecan) in Subjects With Metastatic Breast Cancer

Exclusion Criteria

• •Patients who meet any of the following criteria will be excluded from study entry:
• •1. Treatment with any of the following:
• •* Any systemic anti-cancer chemotherapy, small molecule, biologic, hormonal agent, or immune checkpoint inhibitor therapy from a previous treatment regimen or clinical study within 21 days prior to the first dose of patritumab deruxtecan
• •* Prior treatment with any HER3-targeting agent
• •* Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug treatment
• •* Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug treatment, or palliative radiation therapy within 2 weeks of the first dose of study drug treatment
• •* Chloroquine /hydroxychloroquine ≤14 days prior to the first dose of study drug treatment
• •2. Has any hypersensitivity to drug substances or inactive ingredients in drug product
• •3. Has any history of ILD (including pulmonary fibrosis or radiation pneumonitis), has clinically significant ILD, or is suspected to have such disease by imaging during screening. If imaging findings are unlikely to indicate a history of pneumonitis, then the Investigator should discuss the considerations with the Medical Monitor about potential enrollment and record the reasoning in the source documentation.
• •4. Clinically severe pulmonary compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:
• •* Any underlying pulmonary disorder (e.g., pulmonary emboli, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion)
• •* Any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis)
• •OR prior pneumonectomy
• •5. With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline at the time of starting study treatment. Note: patients with chronic Grade 2 toxicities who are asymptomatic or adequately managed with stable medication may be eligible with approval by the Medical Monitor.
• •6. Leptomeningeal metastases or evidence of spinal cord compression or brain metastases, defined as being clinically active and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Patients with clinically inactive or treated brain metastases who are asymptomatic (i.e., without neurologic signs or symptoms and do not require treatment with corticosteroids or anticonvulsants) may be included in the study. Patients must have a stable neurologic status for at least 2 weeks prior to Cycle 1 Day 1.
• •7. Women who are pregnant, nursing, or plan to become pregnant while in the study and for at least 7 months after the last administration of study treatment
• •8. Men who plan to father a child while in the study and for at least 7 months after the last administration of study treatment
• •9. Uncontrolled or significant cardiovascular disorder prior to Cycle 1 Day 1, including:
• •* Mean resting corrected QT interval using Fridericia's formula (QTcF) prolongation to \>470 ms for females and \>450 ms for males in three successive screening measurements
• •* Patients with a left ventricular ejection fraction (LVEF) \<50%
• •* Resting systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg).
• •* Documented myocardial infarction within 6 months
• •* Congestive heart failure (New York Heart Association ≥ Grade 2 within 28 days
• •10. Has known clinically significant corneal disease from prior therapies such as drug-induced keratitis
• •11. Is receiving chronic systemic corticosteroids dosed at \>10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Patients who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
• •12. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, uncontrolled diabetes mellitus, active bleeding diatheses, or active infection, including hepatitis B, hepatitis C, and human immunodeficiency virus. Screening for chronic conditions is not required.
• •13. Presence of other active invasive cancers other than the one treated in this study within 3 years prior to screening, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix, or other local tumors considered cured by local treatment
• •14. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol
• •15. Patients with HER2+ breast cancer per ASCO-CAP guidelines
• •16. Part A only: Prior treatment with an antibody drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g., trastuzumab deruxtecan, DS-1062a \[datopotamab deruxtecan\], and DS-7300a \[B7-H3 DXd-ADC\])
• •17. Part B patients only: Prior treatment with trastuzumab deruxtecan, sacituzumab govitecan, and/or datopotamab deruxtecan with any of the following:
• •* A severe reaction or severe tolerability issues that necessitated stopping treatment with the therapy
• •* Any unresolved toxicities from the prior therapy greater than Grade 1, with the exception of alopecia
• •18. Treatment with any of the following:
• •* Prior treatment with an antibody drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor except trastuzumab deruxtecan
• •* Prior treatment with trastuzumab deruxtecan within 4 weeks prior to the first dose of patritumab deruxtecan
• •19. Uncontrolled or significant cardiovascular disease, including history of myocardial infarction within 6 months before enrollment
• •20. A severe reaction or severe tolerability issues that necessitated stopping treatment with trastuzumab deruxtecan
• •21. Any unresolved toxicities from prior therapy with trastuzumab deruxtecan