Trial of Trastuzumab Deruxtecan in Previously Treated HER2

NCT06750484 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2000035049
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to test the good and bad effects of a drug called trastuzumab deruxtecan (T-DXd) in adult patients with metastatic HER2-negative breast cancer and which patients might benefit the most from T-DXd.

Conditions

Breast Cancer Metastatic

Keywords

HER2-IHC 0

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The confirmed Objective Response Rate to Trastuzumab Deruxtecan by RECIST (Response Evaluation Criteria In Solid Tumors) defined as the cumulative rate of complete response (CR) rate and partial response (PR) rates, evaluated according to mRECIST v1.1

  After cycle 3, approximately 63 days

Secondary Outcomes (4)

• Objective Response Rate (ORR) Comparison by HER2 Status

  through study completion, an average of 1 year

• Correlation between HER2 protein expression

  Last follow up visit (40 days [+7] from last dose)

• Progression Free Survival (PFS)

  From the date of enrolment to the earliest date of the first objective documentation of radiographic disease progression according to mRECIST version 1.1 or death due to any cause. up to 3 years

• Overall Survival (OS)

  (every 3 months +/-14 days) for up to 3 years

Study Arms (1)

Trastuzumab Deruxtecan

EXPERIMENTAL

T-DXd will be administered intravenously every 3 weeks at a dose of 5.4 mg per kilogram of body weight until disease progression, limiting toxicity, withdrawal of consent, or death. For T-DXd, each cycle of treatment will be 21 days. The number of treatment cycles with T-DXd is not fixed.

Drug: Trastuzumab Deruxtecan

Interventions

Trastuzumab Deruxtecan DRUG

Participants will receive the study drug trastuzumab deruxtecan (T-DXd) by IV infusion every 21 days. The number of treatment cycles will depend on how participants respond to treatment.

Trastuzumab Deruxtecan

Eligibility Criteria

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

You may qualify if:

• Must be competent and able to comprehend, sign, and date an Institutional Review Board (IRB) approved ICF before performance of any study-specific procedures or tests.
• Men or women ≥18 years old.
• Pathologically documented breast cancer that is unresectable or metastatic.
• Tumor biopsies have always shown HER2-IHC 0 (\<10% membrane staining, including 0 null and 0 ultralow) in all prior biopsies and never previously HER2-positive (IHC 3+ or ISH+) or HER2-low (1+, or 2+ ISH-) on prior pathology testing according to American Society of Clinical Oncology College of American Pathologists (ASCO-CAP) guidelines.
• Either HR-positive or HR-negative status of the tumor per ASCO-CAP guidelines are allowed.
• Patients with HR-positive disease must have progressed or be intolerant to CDK 4/6 inhibitors plus endocrine therapy, and patients with HR-negative disease must have received 1 line of therapy in the metastatic setting (progression on or within 6 months of neoadjuvant or adjuvant therapy will be accounted for as 1 line of prior therapy). There is no limit on number of subsequent lines of therapy for study entry. .
• Patients must have never been previously treated with any anti-HER2 therapy, including prior trastuzumab deruxtecan, other HER2-directed ADCs, HER2 antibodies or HER2 tyrosine kinase inhibitors
• Clinical or radiologic progression (during or after most recent treatment) or intolerance to therapy prior to enrollment in this trial
• Adequate archival tumor sample \<3 years-old available for assessment of HER2 status by IHC and by HS-HER2 quantitative assay. If archival tissue is not available or inadequate for assessment (e.g. decalcified bone, cytology, or other), a newly obtained biopsy from a metastatic site (or breast tissue if locally advanced/unresectable disease as the only site of advanced disease) is required on enrolment.
• Presence of at least 1 measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• ECOG PS ≤ 2.
• Left ventricular ejection fraction (LVEF) ≥50% within 28 days prior to C1D1.
• Adequate bone marrow function (Table 1) within 28 days before C1D1, defined as:
• Platelet count \>≥100,000/mm3 (Platelet transfusion is not allowed within 1 week prior to Screening assessment).
• Hemoglobin level ≥9.0 g/dL (red blood cell transfusion is not allowed within 1 week prior to Screening assessment).

You may not qualify if:

• Uncontrolled or significant cardiovascular disease, including any of the following:
• History of myocardial infarction within 6 months before enrolment.
• History of symptomatic congestive heart failure (New York Heart Association Class II to IV).
• Corrected QT interval (QTc) Fridericia prolongation to \>470 ms (females) or \>450 ms (male) based on average of Screening 12 lead ECG.
• Uncontrolled or significant respiratory disease criteria, including any of the following:
• Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
• Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. severe asthma, severe chronic obstructive pulmonary disorder, restrictive lung disease, symptomatic, recurrent and uncontrolled pleural effusion etc.)
• Any autoimmune, connective tissue or inflammatory disorders, including Rheumatoid arthritis, Sjogren's, and sarcoidosis, where there is documented, or a suspicion of pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for participants who are included in the study.
• Prior pneumonectomy (complete)
• Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids to control associated symptoms.
• Subjects with clinically inactive brain metastases may be included in the study.
• Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrolment.
• Has history of another primary malignancy, except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.

Sponsors & Collaborators

• Yale University: lead
• Daiichi Sankyo: collaborator
• AstraZeneca: collaborator

Study Sites (2)

Yale University

New Haven, Connecticut, 06511, United States

RECRUITING

University of Rochester Medical Center

Rochester, New York, 14642, United States

RECRUITING

MeSH Terms

Interventions

trastuzumab deruxtecan

Study Officials

• Adriana Kahn, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Kane

CONTACT

773-369-6904; laura.kane@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All people enrolled in the study will receive the same treatment and no one will receive a placebo or alternate treatment.

Study Record Dates

• First Submitted: December 16, 2024
• First Posted: December 27, 2024
• Study Start: June 20, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)