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

A Phase II Study of U3-1402 (Patritumab Deruxtecan) in Patients With Metastatic Breast Cancer

This study is to evaluate safety and efficacy of an antibody drug conjugate U3-1402 (patritumab deruxtecan) in patients with locally advanced or metastatic breast cancer (MBC).

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer; Locally Advanced Breast Cancer
• Intervention / Treatment: Drug: U3-1402

Detailed Description

U3-1402 (Patritumab Deruxtecan) is an antibody drug conjugate comprising a recombinant fully human anti HER3 monoclonal antibody linked to a linker containing topoisomerase I inhibitor. This is a phase II study of U3-1402 (patritumab deruxtecan) in subjects with MBC. The study will be conducted in 3 parts (Part A , Part B, and Part Z). All enrolled subjects in Part A will undergo pretreatment biopsies to determine if subjects with particular biomarker expression (ER/PR/HER2/HER3) show preliminary efficacy. Part B will enroll subgroups of participants that are metastatic, hormone receptor-positive (HR+) HER2-negative or triple-negative (mTNBC) regardless of HER3 expression that were defined from Part A analysis. Part Z will enroll participants with HER2- positive (HER2+) MBC.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists-South
    • St. Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists-North
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers-Cancer Institute of New Jersey
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
    • Nashville, Tennessee, United States, 37203
      • SCRI Oncology Partners
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Eligibility Criteria:

Inclusion criteria for Part A and B (HER2-negative) and Part Z (HER2-positive) cohorts:

1. Written informed consent, according to local guidelines, signed and dated by the patient or by a legal guardian prior to the performance of any study-specific procedures, sampling, or analyses
2. Women and men at least 18 years-of-age at the time of signature of the informed consent form (ICF)
3. Histologically documented locally advanced or metastatic breast cancer
4. Triple-negative breast cancer (TNBC) patients should have received at least 1 but no more than 5 prior lines of chemotherapy in the metastatic setting
5. Parts A and B patients only: Patients with HR+ HER2-negative MBC should have received prior treatment with endocrine therapy +CDK 4/6 inhibitor. No limit to prior endocrine therapy regimens, but no more than 2 prior chemotherapy regimens in the metastatic setting are allowed. HR+ = Estrogen receptor (ER) and/or Progesterone (PgR) positivity that are defined as ≥1% of cells expressing HR via IHC analysis. HER2 negativity is defined as either of the following: IHC 0, IHC 1+, or IHC 2+/in situ hybridization (ISH) negative.
6. Part B patients only: Patients with HER2-negative MBC will be included into one of the following 2 subgroups: 1) MBC HR+, HER2-, regardless of HER3 expression, who have received trastuzumab deruxtecan and/or sacituzumab govitecan, or, 2) mTNBC, regardless of HER3 expression, who have received sacituzumab govitecan and/or datopotamab deruxtecan.
7. Part Z patients only: should have documented HER2-positive expression as per American Society of Clinical Oncology - College of American Pathologists guidelines based on local testing.
8. Part Z patients only: should have had prior treatment with at least 2 anti-HER2 therapies, 1 of which must be trastuzumab deruxtecan. These patients must have experienced disease progression after receiving trastuzumab deruxtecan.
9. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (bone-only disease excluded)
10. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed ≥4 weeks prior to initiation of study treatment (2 weeks for patients who received palliative radiation therapy), there is no evidence of central nervous system disease progression on a scan or mild neurologic symptoms, and there is no requirement for chronic corticosteroid therapy for the treatment of brain metastases
11. Willingness to undergo pre-treatment biopsy and on-treatment biopsies; must have a tumor amenable to pre-treatment biopsy (unless archived tissue is available and was obtained within 2 months prior to starting treatment) and on-treatment biopsy (excludes bone lesions and previously irradiated lesions)
12. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

13. Has adequate organ function within 7 days before the start of study treatment, defined as:

    • Platelet count ≥100 × 109/L
    • Hemoglobin (Hb) ≥9 g/dL (transfusion and/or growth factor support allowed)
    • Absolute neutrophil count ≥1.5 × 109/L
    • Prothrombin time (PT) and partial thromboplastin time (PTT) ≤1.5 × the upper limit of normal (ULN), except for patients on coumadin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-international normalized ratio (INR) within therapeutic range as deemed appropriate by the Investigator
    • Serum creatinine ≤1.5 × ULN, or creatinine clearance ≥50 mL/min as calculated using the modified Cockcroft-Gault equation; confirmation of creatinine clearance is only required when creatinine is >1.5 × ULN
    • AST/ALT ≤3 × ULN (if liver metastases are present, ≤5 × ULN)
    • Total bilirubin ≤1.5 × ULN if no liver metastases or <3 × ULN in the presence of documented Gilbert's syndrome or liver metastases
    • Serum albumin ≥2.5 g/dL
14. Male patients with female partners of childbearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for at least 7 months following last dose. Male patients must also refrain from donating sperm during their participation in the study.

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from study entry:

Exclusion criteria for Parts A and B (HER2-negative) and Part Z (HER2-positive) cohorts:

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

    Additional exclusion criteria only for Parts A and B (HER2-negative) cohorts:

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

    Additional exclusion criteria only for Part Z (HER2-positive) cohort:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part B; Participants will receive 5.6 mg/kg U3-1402 intravenously on day 1 every 3 weeks. Part B will enroll 20 participants with metastatic hormone-receptor positive (HR+) HER2-negative cancer and 20 participants with metastatic triple-negative breast cancer (mTNBC), regardless of HER3 expression.	Drug: U3-1402; All subjects will receive 5.6 mg/kg U3-1402 (Patritumab Deruxtecan) intravenously on day 1 of every 3 weeks. One cycle is defined as 3 weeks.; Other Names: Patritumab Deruxtecan
Experimental: Part Z; Participants will receive 5.6 mg/kg U3-1402 (Patritumab Deruxtecan) intravenously on day 1 every 3 weeks. Part Z will enroll an additional 21 participants with HER2+ MBC.	Drug: U3-1402; All subjects will receive 5.6 mg/kg U3-1402 (Patritumab Deruxtecan) intravenously on day 1 of every 3 weeks. One cycle is defined as 3 weeks.; Other Names: Patritumab Deruxtecan
Experimental: Part A; Participants will receive 5.6 mg/kg U3-1402 (Patritumab Deruxtecan) intravenously on day 1 every 3 weeks. All participants will undergo pre-treatment biopsies. (An archival tissue sample taken within two months of treatment should be provided if it is not medically feasible to provide a pre-treatment biopsy). Up to 60 HER2-negative participants will be enrolled into this arm.	Drug: U3-1402; All subjects will receive 5.6 mg/kg U3-1402 (Patritumab Deruxtecan) intravenously on day 1 of every 3 weeks. One cycle is defined as 3 weeks.; Other Names: Patritumab Deruxtecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) in Participants With HER2-negative MBC (Part A and Part B)	Overall Response Rate (ORR) is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) out of all treated participants. Confirmed response is two consecutive CR or PR at least 4 weeks apart according to RECIST v1.1 criteria. CR=disappearance of all target and non-target lesions. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of lesion diameters.	Assessed every 6 weeks for the first 6 months then every 9 weeks thereafter until disease progression or death or study discontinuation, up to 45 months.
Progression-Free Survival at 6 Months (PFS-6) in Participants With HER2-negative MBC (Part A and Part B)	Progression-Free Survival at 6 months (PFS-6) is defined as the rate of patients who survive progression-free for at least 6 months per RECIST version (v) 1.1. Per RECIST V1.1, progressive disease is defined as a ≥20% increase in target lesions and ≥5mm increase in size from smallest sum, appearance of any new lesions, or unequivocal progression of non-target lesions.	Assessed every 6 weeks for the first 6 months then every 9 weeks thereafter until disease progression or death or study discontinuation, up to 45 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment- Emergent Adverse Events to Assess Safety and Tolerability	The safety and tolerability of U3-1402 (Patritumab Deruxtecan) was assessed through the analysis of the reported incidence of treatment-emergent AEs. Treatment-emergent AEs are those with an onset on or after the initiation of study therapy up to 40 days after last day of treatment, and will be graded according to NCI CTCAE 5.0.	Every 3 weeks, up to 45 months.
Duration of Response (DOR)	Duration of response (DOR) is calculated only for participants who experienced a Complete Response (CR) or Partial Response (PR) per RECIST V1.1 and is defined as the median number of months of duration from the first documented response [complete response (CR) or partial response (PR)] to the date of disease progression (PD) according to the RECIST V1.1 criteria or death due to any cause. Per RECIST V1.1, CR=disappearance of all target lesions, PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of target lesion diameters, PD is ≥20% increase in target lesions and ≥5mm from smallest sum, appearance of any new lesions, or unequivocal progression of non-target lesions. Kaplan-Meier estimates were used to calculate the 95% confidence intervals for duration of response.	Assessed every 6 weeks for the first 6 months then every 9 weeks thereafter until disease progression or death or study discontinuation, up to 45 months.
Progression-Free Survival (PFS)	Progression Free Survival (PFS) is defined as the time from start of study treatment to the date of the first documented disease progression (PD) according to the RECIST V1.1 criteria or death due to any cause. Per RECIST V1.1, PD is ≥20% increase in target lesions and ≥5mm increase from smallest sum, appearance of any new lesions, or unequivocal progression of non-target lesions.	Assessed every 6 weeks for the first 6 months then every 9 weeks thereafter until disease progression or death or study discontinuation, up to 45 months.
Clinical Benefit Rate (CBR)	CBR is defined as the rate of participants with complete response (CR), partial response (PR), or best overall response of stable disease (SD) for ≥ 6 months according to the RECIST v 1.1 criteria. Per RECIST V1.1: A CR is defined as the disappearance of all target and non-target lesions. A PR is defined as ≥30% decrease in the sum of diameters of target lesions from the baseline sum. A SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).	Assessed every 6 weeks for the first 6 months then every 9 weeks thereafter until disease progression or death or study discontinuation, up to 45 months.
Overall Response Rate (ORR) in Participants With HER2-positive (HER2+) MBC After Progression on Trastuzumab Deruxtecan: Part Z	Overall Response Rate (ORR) is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) out of all treated participants. Confirmed response is two consecutive CR or PR at least 4 weeks apart according to RECIST v1.1 criteria. CR=disappearance of all target and non-target lesions. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of lesion diameters.	Assessed every 6 weeks for the first 6 months then every 9 weeks thereafter until disease progression or death or study discontinuation, up to 45 months.
Progression-Free Survival at 6 Months (PFS-6) in Participants With HER2-positive (HER2+) MBC: Part Z	Progression-Free Survival at 6 months (PFS-6) is defined as the rate of patients who survive progression-free for at least 6 months per RECIST version (v) 1.1. Per RECIST V1.1, progressive disease is defined as a ≥20% increase in target lesions and ≥5mm increase in size from smallest sum, appearance of any new lesions, or unequivocal progression of non-target lesions.	Assessed every 6 weeks for the first 6 months then every 9 weeks thereafter until disease progression or death or study discontinuation, up to 45 months.

Collaborators and Investigators

• Sponsor: SCRI Development Innovations, LLC
• Collaborators: Daiichi Sankyo
• Investigators: Study Chair: Erika Hamilton, MD, SCRI Development Innovations, LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2021
• Primary Completion (Actual): April 9, 2025
• Study Completion (Actual): April 9, 2025

Study Registration Dates

• First Submitted: January 5, 2021
• First Submitted That Met QC Criteria: January 5, 2021
• First Posted (Actual): January 7, 2021

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Metastatic breast cancer; Triple Negative Breast Cancer; Breast Neoplasm; locally advanced breast cancer; Hormone Receptor Positive Breast Cancer; HER3 Expression
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; patritumab deruxtecan
• Other Study ID Numbers: BRE 354

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No