TRUDI: TDXD+Durva in HER2+/Low IBC

NCT05795101 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-544
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to test the safety and effectiveness of an investigational drug combination (trastuzumab deruxtecan and durvalumab) to learn whether the intervention works in treating Human Epidermal growth factor Receptor-2 (HER2)-expressing inflammatory breast cancer. The names of the study drugs involved in this study are:

• Trastuzumab deruxtecan
• Durvalumab

Conditions

Invasive Breast Cancer; Inflammatory Breast Cancer Stage III; HER2-positive Breast Cancer; HER2 Low Breast Adenocarcinoma; Breast Cancer

Keywords

Invasive Breast Cancer; Inflammatory Breast Cancer Stage III; HER2-positive Breast Cancer; HER2 Low Breast Adenocarcinoma; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) Rate

  pCR rate is the proportion of participants with absent invasive carcinoma in the breast and lymph nodes at time of surgery; in situ disease only is considered pCR; if off-treatment prior to surgery than considered not pCR.

  Assessed on surgical tissue: surgery occurs no later than 6 weeks post 8 cycles of neo-adjuvant therapy (one cycle=21 days)

Secondary Outcomes (3)

• Residual Cancer Burden (RCB) Response

  Assessed on surgical tissue; surgery occurs +day 14 and no later than 6 weeks post 8 cycles of neo-adjuvant therapy (one cycle=21 days)

• Event Free Survival (EFS)

  Disease assessed every 6 weeks by chest xray (+/- 1 week) until completion of 8 cycles of neo-adjuvant therapy (one cycle=21 days); Follow-up assessments post-surgery every 6 months (+/- 8 weeks) until participant withdrawal or death up to 4 years

• Distant progression or distant disease-free survival (DP/DDFS)

  Disease assessed every 6 weeks by chest xray (+/- 1 week) until 8 cycles of neo-adjuvant therapy (one cycle=21 days); Follow-up assessments post-surgery every 6 months (+/- 8 weeks) until participant withdrawal or death up to 4 years

Study Arms (2)

HER2 Positive

EXPERIMENTAL

Participants will be enrolled into one of two cohorts: HER2 positive IBC (cohort 1) and HER2 low IBC (cohort 2). * HER2-positive determined locally by the current ASCO/CAP guidelines * Participants will receive trastuzumab deruxtecan plus durvalumab for eight cycles prior to surgery. (Cycle Length is 21 days) * After surgery, Participants will receive therapy per physician's choice and to reflect current standard of care.

Drug: Trastuzumab deruxtecan; Drug: Durvalumab

HER2-Low

EXPERIMENTAL

Participants will be enrolled into one of two cohorts: HER2 positive IBC (cohort 1) and HER2 low IBC (cohort 2) * HER2-low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested) * Participants will receive trastuzumab deruxtecan plus durvalumab for eight cycles prior to surgery (Cycle Length is 21 days) * After surgery, Participants will receive therapy per physician's choice and to reflect current standard of care.

Drug: Trastuzumab deruxtecan; Drug: Durvalumab

Interventions

Trastuzumab deruxtecan DRUG

via IV, protocol determined dosage once per cycle up to eight cycles. Each cycle will last for 21 days (three weeks).

Also known as: Enhertu

HER2 Positive; HER2-Low

Durvalumab DRUG

via IV, protocol determined dosage once per cycle up to eight cycles. Each cycle will last for 21 days (three weeks).

HER2 Positive; HER2-Low

Eligibility Criteria

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

You may qualify if:

• Participants must have a histological or cytological diagnosis of invasive breast cancer.
• All histologic subtypes are eligible.
• Participants must have a clinical diagnosis of stage III inflammatory breast cancer within the past 6 months
• HER2-positive status as determined locally by the current ASCO/CAP guidelines or HER2-low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested) (note: ISH may be determined by either fluorescence in situ hybridization \[FISH\] or dual in situ hybridization \[DISH\])
• Any ER and PR expressions are permitted but must be known
• Participants must be treatment-naïve
• Participants must agree to undergo two research biopsies of the tumor (if safely accessible, as determined by the treating investigator): at baseline (prior to the first treatment) and after the first week of treatment on C1D8. Previously collected archival tissue will also be obtained on all participants. For participants for whom the tumor is not safely accessible, this archival tissue needs to be located and availability confirmed at time of registration.
• Pre- and postmenopausal women or male patients ≥ 18 years of age
• ECOG performance status 0-1 (Karnofsky \> 60%, see Appendix A).
• LVEF ≥ 50% within 28 days prior to enrollment
• Participants must have normal organ and marrow function prior to enrollment as defined below:
• Absolute neutrophil count ≥2,000/mcL
• Platelets ≥100,000/mcL
• Hemoglobin ≥ 9.0 g/dl
• INR/PT/aPTT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is in therapeutic range of anticoagulant

You may not qualify if:

• Has received prior systemic anti-cancer therapy for the current diagnosis of inflammatory breast cancer, including chemotherapy, immunotherapy, or targeted therapy
• Has received any radiotherapy or surgery for the current diagnosis of inflammatory breast cancer. Tumor biopsies are not considered surgery for the purpose of enrollment.
• Prior hypersensitivity to durvalumab or the excipients of durvalumab or trastuzumab deruxtecan or history of severe hypersensitivity reactions to other monoclonal antibodies.
• Major surgery within 4 weeks prior to study treatment initiation. Patients must have recovered from any effects of any major surgery.
• Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
• Participant has a medical condition that requires chronic systemic steroid therapy (\> 10 mg of prednisone daily or equivalent) or any other form of immunosuppressive medication (including disease modifying agents) and has required such therapy in the last 2 years. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic therapy.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, Wegener syndrome \[granulomatosis with polyangiitis\], Graves' disease, and rheumatoid arthritis, hypophysitis, uveitis, etc). The following are exceptions to this criterion:
• \-- Patients with vitiligo or alopecia, Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement, Patients with any chronic skin condition that does not require systemic therapy, Patients with celiac disease controlled by diet alone, who may also be included, but only after consultation with the Principal Investigator, Patients without active disease in the last 5 years, who may also be included but only after consultation with the Principal Investigator
• History of (non-infectious) 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 (ie, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis etc.), and prior pneumonectomy
• Corrected QT interval (QTcF) prolongation to \> 470 msec on screening EKG
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval
• Any of the following procedures or conditions in the 6 months prior to enrollment: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure (New York Heart Association Functional Classification Grade ≥2), and stroke. Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial infarction related symptoms, should have a cardiology consultation before enrollment to rule out myocardial infarction.
• Cardiac ejection fraction outside institutional range of normal or \<50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition \[MUGA\] scan if an echocardiogram cannot be performed or is inconclusive).
• 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 study treatment and of low potential risk for recurrence. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, Adequately treated carcinoma in situ without evidence of disease

Sponsors & Collaborators

• Filipa Lynce, MD: lead
• AstraZeneca: collaborator
• Daiichi Sankyo: collaborator

Study Sites (3)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• RCB calculator from M.D. Anderson for secondary outcome measure

MeSH Terms

Conditions

Inflammatory Breast Neoplasms; Breast Neoplasms

Interventions

trastuzumab deruxtecan; durvalumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Filipa Lynce, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Filipa Lynce, MD

CONTACT

(617) 632-3800; filipa_lynce@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Model Details: two parallel cohorts

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: April 3, 2023
• Study Start: May 4, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2032
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)