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

NCT04699630 | Completed Phase 2 Results FDA Drug

• 1 other identifier: BRE 354
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 11

Brief Summary

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).

Conditions

Locally Advanced Breast Cancer; Metastatic Breast Cancer

Keywords

Breast Neoplasm; HER3 Expression; Hormone Receptor Positive Breast Cancer; Triple Negative Breast Cancer; Metastatic breast cancer; locally advanced breast cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Incidence of Treatment- Emergent Adverse Events to Assess Safety and Tolerability

  Every 3 weeks, up to 45 months.

• Duration of Response (DOR)

  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)

  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)

  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

  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.

Study Arms (3)

Part A

EXPERIMENTAL

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

Part B

EXPERIMENTAL

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

Part Z

EXPERIMENTAL

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

Interventions

U3-1402 DRUG

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.

Also known as: Patritumab Deruxtecan

Part A; Part B; Part Z

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Women and men at least 18 years-of-age at the time of signature of the informed consent form (ICF)
• Histologically documented locally advanced or metastatic breast cancer
• 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
• 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.
• 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.
• 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.
• 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.
• At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (bone-only disease excluded)
• 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
• 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)
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• 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)

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• 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
• Has any hypersensitivity to drug substances or inactive ingredients in drug product
• 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.
• 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
• 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.
• 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.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Daiichi Sankyo: collaborator

Study Sites (11)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Florida Cancer Specialists-South

Fort Myers, Florida, 33901, United States

Location

Florida Cancer Specialists-North

St. Petersburg, Florida, 33705, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rutgers-Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

patritumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Sarah Cannon Development Innovations, LLC
• Organization: Sarah Cannon Development Innovations, LLC

SCRI.InnovationsMedical@scri.com

615-329-7274

Study Officials

• Erika Hamilton, MD

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2021
• First Posted: January 7, 2021
• Study Start: May 3, 2021
• Primary Completion: April 9, 2025
• Study Completion: April 9, 2025
• Last Updated: May 22, 2026
• Results First Posted: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)