NCT07371585

Trastuzumab Deruxtecan in First-Line HER2-Positive Metastatic Breast Cancer With Proactive Toxicity Management

Patient-Centered Study of Trastuzumab Deruxtecan (T-DXd) in First-Line HER2-Positive Metastatic Breast Cancer With Proactive Toxicity Management Reflecting Real-World Clinical Practice

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 300 (estimated)
• Sponsor: SOLTI Breast Cancer Research Group · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, single arm, non-randomized, multicenter, phase 2 study assessing the efficacy and safety of T-DXd as first-line treatment in HER2-positive advanced/metastatic BC patients (N=300). The study integrates digital health tools for proactive toxicity management and potentially facilitate early detection of ILD/pneumonitis.

Detailed description

\*Study Population\* The study will enroll male or pre/post-menopausal women aged ≥ 18 years with locally advanced or metastatic HER2-positive (IHC 3+ or ISH+, by local testing) BC who have not received prior chemotherapy or HER2-targeted therapy for advanced/metastatic disease. Eligible patients should have evaluable disease (measurable and not measurable) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Patients with active and treated CNS metastases not requiring immediate local therapy are eligible. \*Study Interventions \* Patients meeting all eligibility criteria will receive T-DXd at 5.4 mg/kg administered as IV infusion q3w in combination with pertuzumab at a loading dose of 840 mg on Day 1 of Cycle 1, followed by 420 mg in subsequent cycles, administered as IV q3w. Treatment will be administered continuously until RECIST 1.1-defined progressive disease, unacceptable toxicity, investigator's decision, withdrawal of consent, or other reasons described in the protocol. T-DXd rechallenge will be allowed for patients who discontinued T-DXd for reasons other than progressive disease, grade ≥2 ILD or any toxicity requiring permanent discontinuation per T-DXd SmPC and/or protocol-defined management guidelines, and who have progressed to maintenance treatment. Standard endocrine therapy (aromatase inhibitor, fulvestrant or tamoxifen) administered concurrently with the study treatment (from C1D1) is allowed for patients with HR-positive tumors, as per local practice. For men and premenopausal women, LHRH agonist is allowed as per local practice. Patients will be followed via digital health tools. These consist of one mobile app and two devices: * Digital health mobile app (CANKADO or Resilience depending on the country and site \[used in accordance with respective CE markings\]) accessed through the patient's phone and offering: * Remote (Resilience PRO) or automated (CANKADO PRO-react) patient monitoring through electronic patient-reported outcomes (ePROs). * Comprehensive educational content with a focus on managing study treatment-related toxicities. * Optional self-management programs to support patient autonomy, including cognitive behavioral therapy for fatigue, adapted physical activity, and meditation (Resilience only). * A pulse oximeter that together with the digital health mobile app will allow self-tracking of vital parameters such as oxygen saturation and heart rate, potentially facilitating early ILD detection. * A smartwatch to collect patient granular data. \*Study Assessments \* Imaging will be performed prior to day 1 of treatment and target and non-target lesions will be identified as per RECIST v.1.1. Tumor assessments will be performed every 9 weeks for the first 12 months from start of treatment and then every 12 weeks until disease progression, withdrawal of consent, death, or the end of the study, whichever occurs the first. Tumor assessments will be performed on the specified schedule regardless of treatment delays. Tumor response will be assessed as per RECIST v.1.1. A Formalin-Fixed Paraffin Embedded (FFPE) specimen from metastatic disease (preferably) with adequate quantity and quality of tumor tissue must be provided (tumor block) prior to treatment. Samples will be tested to confirm quality at the central lab prior to enrollment. Remaining tissue will be kept at the central lab for retrospective HER2 central confirmation and additional biomarkers of response. A tumor biopsy will be also performed at disease progression. Blood samples (for biomarkers) will be collected at C1D1, C2D1 and at disease progression for exploratory objectives. Patients that discontinue for reasons other than progressive disease, ILD/pneumonitis ≥ Grade 2 or any toxicity requiring permanent discontinuation per T-DXd SmPC and/or protocol-defined management guidelines, will go through a structured interview at the moment of T-DXd discontinuation. This structured interview will collect information from both the healthcare professional and the patient at that time to understand the main reasons for T-DXd discontinuation and if the patient is deemed "suitable" or "not suitable" for T-DXd rechallenge. This interview will also be conducted before treatment restart. Blood samples will be collected at C1D1, C2D1 and disease progression during T-DXd rechallenge. A blood sample will be collected from each patient at C2D1 to obtain germline DNA for Pharmacogenomic analyses. PRO instruments will be completed by patients to evaluate the treatment impact from the patient's perspective. All patients will be closely monitored for adverse events (AEs) throughout the study. The incidence, nature, and severity of AEs and laboratory abnormalities will be graded per the NCI CTCAE v.5.0. Laboratory safety assessments will include the regular monitoring of hematology, serum chemistry, oxygen saturation and pregnancy test. Oxygen saturation and heart rate will also be monitored once a day by the digital health tools. Primary prophylaxis for the prevention of nausea and vomiting with a combination of three (3) antiemetic agents (e.g., dexamethasone with either a 5 HT3 receptor antagonist and/or an NK1 receptor antagonist, as well as other medicinal products as indicated) is mandatory.

Conditions

• Breast Cancer Stage IV

Interventions

Type	Name	Description
DEVICE	Digital Health Tools	Patients will be followed via digital health tools for proactive toxicity management, which consist of one mobile app and two devices: (1) CANKADO/Resilience app (depending on the country and site) accessed through the patient's phone; (2) A pulse oximeter that together with the digital health mobile app will allow self-tracking of vital parameters such as oxygen saturation and heart rate, potentially facilitating early ILD detection; and (3) A smartwatch to collect patient granular data. All three digital health tools/items are CE-marked medical devices, where relevant, used exclusively within their approved intended purpose, and not subject to any investigation of safety or performance within this study.
DRUG	T-DXd	T-DXd at 5.4 mg/kg will be administered as IV infusion q3w.
DRUG	Pertuzumab	Pertuzumab will be administered at a loading dose of 840 mg on Day 1 of Cycle 1, followed by 420 mg in subsequent cycles, administered as IV q3w.

Timeline

• Start date: 2026-02-18
• Primary completion: 2029-08-01
• Completion: 2030-07-01
• First posted: 2026-01-28
• Last updated: 2026-03-27

Locations

27 sites across 3 countries: France, Germany, Spain