Phase II Trial of TRAstuzumab deruxtecaN in firSt-line Treatment of HER2-positive Locally advanCEd or Metastatic Breast caNcer (MBC) Patients Considered Resistant to Trastuzumab + Pertuzumab + Taxane Due to Early Relapse."TRANSCENDER Study"

Plain English Summary

Trastuzumab Deruxtecan in First-line HER2-positive Locally Advanced/MBC Patients Resistant to Trastuzumab+Pertuzumab is a Phase 2 clinical trial sponsored by Spanish Breast Cancer Research Group studying Locally Advanced Breast Cancer, Metastatic Breast Cancer. This trial tests the drug Trastuzumab deruxtecan (T-DXd) in patients with HER2-positive breast cancer that has spread or cannot be removed. It is for patients whose cancer has returned or progressed after treatment with trastuzumab, pertuzumab, and a taxane chemotherapy. Participation involves receiving T-DXd intravenously every 3 weeks until the cancer progresses, toxicity occurs, or the patient withdraws consent. Alternative treatments may include other chemotherapy, targeted therapies, or hormone therapy depending on the specific cancer characteristics. The trial aims to enroll 2 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients must be at least 18 years old with HER2-positive locally advanced or metastatic breast cancer. They must have previously received treatment with trastuzumab, pertuzumab, and a taxane, and their cancer must have returned or progressed. Patients must have good overall health, with adequate organ and bone marrow function, and a heart function (LVEF) of at least 50%. Patients with active brain metastases or certain lung conditions may not be eligible. This trial is studying Locally Advanced Breast Cancer, Metastatic Breast Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how well the new drug shrinks tumors, indicating its effectiveness in fighting the cancer. The specific primary outcome measures are: Objective Response Rate (ORR) (Through study treatment, and average of 18 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for patients with HER2-positive breast cancer that has become resistant to current standard therapies, offering a potential new treatment option. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Locally Advanced Breast Cancer, Metastatic Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial investigates a targeted therapy for a specific breast cancer subtype, representing a growing area in oncology drug development with potential for significant market impact if successful. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if your cancer is HER2-positive and if you have received the specific prior treatments mentioned. Understand that treatment involves regular IV infusions and ongoing monitoring for side effects and cancer progression. Be prepared for regular clinic visits for infusions, blood tests, scans, and to discuss any side effects with your medical team. The trial is being conducted at 19 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 2 participants

Interventions

• DRUG: Trastuzumab deruxtecan — 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 discontinuat

Primary Outcomes

• Objective Response Rate (ORR) (Through study treatment, and average of 18 months)

Secondary Outcomes

• 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)

Full Eligibility Criteria

Inclusion Criteria:

1. Written and signed informed consent obtained prior to any study-specific procedure.
2. Male or female patients of at least 18 years of age.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
4. Life expectancy ≥ 12 weeks.
5. Recurrent breast cancer that is unresectable locally advanced or metastatic.
6. 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.
7. 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.
8. 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.
9. Measurable disease assessed by the investigator based on RECIST version 1.1.
10. Left ventricular ejection fraction (LVEF) ≥ 50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
11. Adequate organ and marrow function defined as follows:

    1. Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 (1.5x109/L).
    2. Platelet count ≥ 100,000/mm3 (100x109/L).
    3. Hemoglobin ≥ 9g/dL (90g/L).
    4. Creatinine clearance ≥ 30 mL/min as calculated using the standard method for the institution.
    5. Total serum bilirubin ≤ 1.5 × upper limit of normal (ULN) if no liver metastases or \< 3 × ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.
    6. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 3.0 x ULN (\< 5.0 × ULN in participants with liver metastases).
    7. Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5.0 x ULN if bone or liver metastases are present).
    8. Serum albumin ≥ 2.5 g/dL
12. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN.
13. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
14. Negative serum pregnancy test with a sensitivity of at least 25 milliInternational Units per milliliter of urine (mIU/mL) (unless permanent previous sterilization procedure such as bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) for premenopausal women, and for women who have experienced menopause onset \< 12 months prior to first dose of therapy.

Exclusion Criteria:

1. 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).
2. Ineligible for treatment with T-DXd.
3. Any substance abuse or other medical conditions that, in the investigator's opinion, may interfere with patient's participation or study results.
4. 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.
5. Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
6. Lung criteria:

   1. 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.).
   2. 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.
   3. Prior pneumonectomy.
7. 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)

Trial Locations

• Hospital Universitario de Jeréz De La Frontera, Cadiz, Andalusia, Spain
• Hospital Universitario de Jaén, Jaén, Andalusia, Spain
• Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain
• Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain
• Hospital Universitario Puerta de Hierro de Majadahonda, Majadahonda, Madrid, Spain
• Hospital Universitario Son Espases, Palma de Mallorca, Mallorca, Spain
• Hospital Galdakao-Usansolo, Galdakao, Vizcaya, Spain
• Complejo Hospitalario Universitario A Coruña (CHUAC), A Coruña, Spain
• Hospital San Juan de Alicante, Alicante, Spain
• Hospital Universitario de Badajoz, Badajoz, Spain
• ...and 9 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Metastatic Breast Cancer
• HER2-positive Breast Cancer
• Locally Advanced Breast Cancer
• Trastuzumab Resistance
• Pertuzumab Resistance
• Taxane Resistance
• Oncology
• Targeted Therapy
• Chemotherapy

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