Trastuzumab Deruxtecan in First-line HER2-positive Locally Advanced/MBC Patients Resistant to Trastuzumab+Pertuzumab

NCT05744375 | Terminated Phase 2 Results

• 2 other identifiers: GEICAM/2021-082023-503627-26-00
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 19

Brief Summary

The goal of this national, multicenter single arm phase II clinical trial is to study the efficacy, safety and tolerability of the administration of Trastuzumab Deruxtecan (T-DXd) in HER2-positive locally advanced or metastatic breast cancer (MBC) patients resistant to trastuzumab plus pertuzumab plus taxane due to early relapse. The main questions it aims to answer are:

• To evaluate the antitumor activity of T-DXd in the first-line treatment of HER2-positive breast cancer patients resistant to trastuzumab-pertuzumab based therapy.
• To assess other efficacy measures.
• To evaluate safety and tolerability in all patients enrolled in the study.
• To evaluate health-related quality of life (HRQoL). Forty-one evaluable patients will be treated with trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV every 3 weeks (± 3 days). Patients will receive T-DXd until unacceptable toxicity, progressive disease, informed consent withdrawal, or other discontinuation criterion is met.

Conditions

Locally Advanced Breast Cancer; Metastatic Breast Cancer

Keywords

Trastuzumab deruxtecan; HER2-positive; Advanced Breast Cancer; Metastatic Breast Cancer; resistant to prior (neo) adjuvant anti-HER2 therapy.

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective Response Rate (ORR) is defined as the rate of complete response (CR) plus partial response (PR) based on the investigator's assessment using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1., out of the patients who received at least 1 dose of treatment (efficacy population). Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an \>=30% decrease in the sum of the longest diameter of target lesions. The ORR will be reported, including a 95% Confidence Interval (CI) using the Clopper-Pearson method. A sensitivity analysis will be performed using the Intent to treat population (ITT) population.

  Through study treatment, and average of 18 months

Secondary Outcomes (7)

• Progression-Free Survival (PFS)

  Through study treatment, and average of 18 months

• Overall Survival (OS)

  Through study, and average of 36 months

• Time to Treatment Response (TTR)

  Through study treatment, and average of 18 months

• Duration of Response (DoR)

  Through study treatment, and average of 18 months

• The Number of Participants Who Experienced Adverse Events (AE) Related to Study Treatment

  Through study treatment, and average of 18 months

Other Outcomes (2)

• Progression-Free Survival 2 (PFS2)

  Through study, and average of 36 months

• Progression-Free Survival 3 (PFS3)

  Through study, and average of 36 months

Study Arms (1)

Trastuzumab deruxtecan (T-DXd)

EXPERIMENTAL

All patients enrolled will be treated with trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV every 3 weeks (± 3 days). The subject's weight at baseline will be used to calculate the initial dose. If during the course of treatment the subject's weight changes by ± 10% of the baseline weight, the subject's dose will be recalculated based on the subject's updated weight. Patients will receive T-DXd until unacceptable toxicity, progressive disease (PD), informed consent withdrawal, or other discontinuation criterion is met.

Drug: Trastuzumab deruxtecan

Interventions

Trastuzumab deruxtecan DRUG

All patients enrolled will be treated with trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV every 3 weeks (± 3 days). The subject's weight at baseline will be used to calculate the initial dose. If during the course of treatment the subject's weight changes by ± 10% of the baseline weight, the subject's dose will be recalculated based on the subject's updated weight. Patients will receive T-DXd until unacceptable toxicity, progressive disease (PD), informed consent withdrawal, or other discontinuation criterion is met.

Also known as: Enhertu

Trastuzumab deruxtecan (T-DXd)

Eligibility Criteria

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

You may qualify if:

• Written and signed informed consent obtained prior to any study-specific procedure.
• Male or female patients of at least 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
• Life expectancy ≥ 12 weeks.
• Recurrent breast cancer that is unresectable locally advanced or metastatic.
• Pathologically documented HER2-positive status by local laboratory determination, preferably on the most recent available Formalin-fixed paraffin-embedded (FFPE) tumor sample, according to the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) international guidelines valid at the time of the assay. In case of discordance in HER2 status in different biopsies, the result from the most recent biopsy will be used.
• Pathologically documented Hormone Receptor (HR)-positive or -negative by local laboratory determination, preferably on the most recent available FFPE tumor sample, and according to ASCO/CAP international guidelines valid at the time of the assay. In case of discordance in HR status in different biopsies, the result from the most recent biopsy will be used.
• Prior anti-HER2 based therapy (with trastuzumab plus pertuzumab plus taxane with or without trastuzumab-emtansine) in the (neo)adjuvant setting with a relapse while on therapy or within 12 months from the end of last anti-HER2 therapy.
• Measurable disease assessed by the investigator based on RECIST version 1.1.
• Left ventricular ejection fraction (LVEF) ≥ 50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
• Adequate organ and marrow function defined as follows:
• Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 (1.5x109/L).
• Platelet count ≥ 100,000/mm3 (100x109/L).
• Hemoglobin ≥ 9g/dL (90g/L).
• Creatinine clearance ≥ 30 mL/min as calculated using the standard method for the institution.

You may not qualify if:

• Prior chemotherapy or HER2-targeted therapy for locally advanced or MBC (one prior endocrine therapy regimen for MBC without concurrent anti-HER2 therapy or radiotherapy is allowed).
• Ineligible for treatment with T-DXd.
• Any substance abuse or other medical conditions that, in the investigator's opinion, may interfere with patient's participation or study results.
• Patients with spinal cord compression, leptomeningeal disease or clinically active central nervous system (CNS) metastases. Participants with clinically inactive brain metastases or treated brain metastases that are no longer symptomatic, and no needing corticosteroids or anticonvulsants may be enrolled in the study.
• Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• Lung criteria:
• Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within three months of the study enrollment, severe asthma, severe Chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion etc.).
• Any autoimmune, connective tissue or inflammatory disorders (e.g. Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) 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 electronic Case Report Form (eCRF) for patients who are enrolled in the study.
• Prior pneumonectomy.
• Medical history of myocardial infarction within 6 months before registration, symptomatic congestive heart failure (CHF), troponin levels consistent with myocardial infarction as defined according to American College of Cardiologists (ACC) guidelines, unstable angina, or serious cardiac arrhythmia requiring treatment. QT interval corrected using Fridericia's formula (QTcF) \> 470 msec (females) or \> 450 msec (males) based on average of the screening triplicate 12-lead ECG.
• History of active primary immunodeficiency, known Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
• Patients who received before treatment starts:
• Any investigational agent within 4 weeks.
• Chemotherapy within a period of time that is shorter than the cycle duration used for that treatment (e.g. \< 3 weeks for fluorouracil, doxorubicine, epirubicin or \< 1 week for weekly chemotherapy).
• Targeted therapy (e.g., antibodies): up to 4 weeks prior to starting study treatment.

Sponsors & Collaborators

• Spanish Breast Cancer Research Group: lead
• AstraZeneca: collaborator

Study Sites (19)

Hospital Universitario de Jeréz De La Frontera

Cadiz, Andalusia, 11407, Spain

Location

Hospital Universitario de Jaén

Jaén, Andalusia, 23007, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario de Fuenlabrada

Fuenlabrada, Madrid, 28942, Spain

Location

Hospital Universitario Puerta de Hierro de Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Son Espases

Palma de Mallorca, Mallorca, 07120, Spain

Location

Hospital Galdakao-Usansolo

Galdakao, Vizcaya, 48960, Spain

Location

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, 15006, Spain

Location

Hospital San Juan de Alicante

Alicante, 03550, Spain

Location

Hospital Universitario de Badajoz

Badajoz, 06080, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario San Pedro de Alcántara

Cáceres, 10003, Spain

Location

Hospital Universitario Clínico San Cecilio

Granada, 18016, Spain

Location

Hospital Universitario Arnau de Vilanova de Lleida

Lleida, 25198, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Related Links

• Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group

MeSH Terms

Conditions

Breast Neoplasms

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Recruitment for the study was closed on January 17, 2025, due to insufficient accrual (only two patients were included), and the sponsor decided on its premature termination.

Results Point of Contact

• Title: Scientific Director / Medical Lead / Project Manager
• Organization: Spanish Breast Cancer Research Group (GEICAM)

geicam@geicam.org

+34916592870

Study Officials

• Study Director Study Director

  Hospital General Universitario Gregorio Marañón. Madrid, Spain.

  STUDY DIRECTOR

• Study Director Study Director

  Hospital del Mar. Barcelona, Spain.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: February 15, 2023
• First Posted: February 27, 2023
• Study Start: September 28, 2023
• Primary Completion: July 17, 2025
• Study Completion: July 17, 2025
• Last Updated: April 2, 2026
• Results First Posted: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (19)