A Randomized Secondary Adjuvant Treatment Intervention Study Comparing Trastuzumab-Deruxtecan to SOC Therapy in eBC Patients With Molecular Relapse

NCT06643585 | Recruiting Phase 3

• 2 other identifiers: SURVIVE HERoes2024-516173-76-00
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Prospective, multi-center, randomized, open label comparative Phase III study in patients with intermediate to high-risk (as defined in the SURVIVE trial) HER2-positive or HER2-low early breast cancer, who participate in the SURVIVE trial and experience a molecular relapse, as assessed based on a positive circulating tumor DNA (ctDNA) result, with 2:1 allocation to:

• Arm A: Trastuzumab-Deruxtecan (i.v. 5,4 mg/kg, q3w) + endocrine therapy (if hormonal-receptor-positive) for 16 cycles or until relapse, if earlier
• Arm B: Continuous treatment of physician's choice (may include endocrine treatment, CDK4/6-Inhibition, T-DM1, Olaparib, Trastuzumab, Pertuzumab, Capecitabine or Neratinib)

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• ctDNA clearance rate 12 months after randomization

  To compare ctDNA clearance rate twelve months after randomization between patients in the experimental arm (Arm A) versus patients in the standard of care arm (Arm B). ctDNA is measured as per RaDaR assay (see 5.8). Endpoint: ctDNA clearance rate is defined as the proportion of patients with a ctDNA negative blood test result at a given time point: (Patients with negative cfDNA at 12 months)/(all patients)

  from enrollment to end of treatment after 12 months

Study Arms (2)

Arm A

EXPERIMENTAL

Trastuzumab-Deruxtecan (i.v. 5,4 mg/kg, q3w) + endocrine therapy (if hormonal-receptor-positive) for 16 cycles or until relapse, if earlier

Drug: Trastuzumab-Deruxtecan

Arm B

ACTIVE COMPARATOR

Continuous treatment of physician's choice (may include endocrine treatment, CDK4/6-Inhibition, T-DM1, Olaparib, Trastuzumab, Pertuzumab, Capecitabine or Neratinib)

Other: Physicians Choice (PhC).

Interventions

Trastuzumab-Deruxtecan DRUG

Trastuzumab-Deruxtecan (i.v. 5,4 mg/kg, q3w) + endocrine therapy (if hormonal-receptor-positive) for 16 cycles or until relapse, if earlier

Arm A

Physicians Choice (PhC). OTHER

Continuous treatment of physician's choice (may include endocrine treatment, CDK4/6-Inhibition, T-DM1, Olaparib, Trastuzumab, Pertuzumab, Capecitabine or Neratinib)

Arm B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be eligible for study participation if they comply with the following criteria:
• Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures.
• Females or males, ≥ 18 years and ≤ 75 years of age.
• Invasive breast carcinoma as revealed by local pathology that is either:
• HER2-positive defined as an immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH) in Her2 2+ tumors (as defined in 2018 American Society of Clinical Oncology - College of American Pathologists \[ASCO-CAP\] guidelines)
• HER2-low defined as an immunohistochemistry (IHC) score of 1+ or an IHC score of 2+ with a mandatory negative in situ hybridization (ISH), as defined in 2018 American Society of Clinical Oncology - College of American Pathologists \[ASCO-CAP\] guidelines.
• Complete resection of the tumor with resection margins free of invasive carcinoma (R0).
• Participation in the SURVIVE study and evidence of molecular relapse (as assessed based on a positive ctDNA result obtained in the SURVIVE-study)
• No evidence of metastatic relapse as revealed by a CT-scan (Abdomen/Chest) and a SPECT bone scan that must be performed within 8 weeks before randomization (M0).
• Completion of surgery, (neo-)adjuvant chemotherapy (if applicable) and radiation therapy (if applicable, whichever occurred last) at least 6 months before randomization.
• Adjuvant/Postneoadjuvant treatment with Trastuzumab, Pertuzumab, T-DM1, Capecitabine, Pembrolizumab, and Olaparib must be discontinued upon randomization into Arm A (treatment with trastuzumab deruxtecan). The washout periods (see Table 2) must be complied with. Endocrine therapy (i.e. Tamoxifen, Letrozol, Anastrozol, Fulvestrant or Exemestane) can be administered simultaneously to treatment with trastuzumab deruxtecan.
• Known HR status, per local laboratory assessment, as defined by ASCO-CAP guidelines (≥1%): HR-positive status defined by either positive estrogen receptor (ER) and/or positive progesterone receptor (PR) status. HR-negative status defined by both known negative ER and known negative PR
• Left ventricular ejection fraction (LVEF) ≥50% within 28 days prior to randomization
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at Screening
• Adequate organ and bone marrow function within 28 days before randomization as described in table 1. Organ and bone marrow function criteria must also be met when laboratory tests are repeated within 3 days before Cycle 1 Day 1. Transfusion (red blood cell or platelet) or G-CSF administration is not allowed within 2 weeks prior to the day on which marrow function is assessed.

You may not qualify if:

• Stage IV (metastatic) breast cancer.
• Patients with a history of any secondary primary malignancy are ineligible with the following exceptions:
• ipsi- or contralateral non-invasive carcinoma of the breast (DCIS)
• other, curatively treated in-situ disease
• adequately treated non-melanoma carcinoma of the skin
• Prior treatment with T-DXd.
• Combination of T-DXd with any other anti-cancer treatment is not permitted, except for endocrine therapy.
• Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
• Patients with a medical history of myocardial infarction (MI) within 6 months before first exposure to study intervention, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out MI.
• Corrected QT interval (QTcF) prolongation to \> 470 msec (females) or \> 450 msec (males) based on average of the screening triplicate 12-lead ECG.
• History of (non-infectious) Interstitial lung disease (ILD) / pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
• Active primary immunodeficiency, known uncontrolled active HIV infection or active hepatitis B or C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Subjects should be tested for HIV prior to randomization/enrolment if required by local regulations or institutional review board (IRB)/ethics committee (EC).
• Lung criteria:
• Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (for example pulmonary emboli within three months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.)

Sponsors & Collaborators

• Prof. Wolfgang Janni: lead

Study Sites (1)

University Clinic Ulm

Ulm, 89075, Germany

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Wolfgang Janni, Prof. Dr. med.

CONTACT

+49731 500 58536; studienzentrale.ufk@uniklinik-ulm.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med. Wolfgang Janni

Study Record Dates

• First Submitted: October 10, 2024
• First Posted: October 16, 2024
• Study Start: April 22, 2025
• Primary Completion (Estimated): April 22, 2032
• Study Completion (Estimated): April 22, 2032
• Last Updated: May 2, 2025

Record last verified: 2025-04

Locations

DE (1)