HER2DX-guided diagnostic treatment For patients with HER2-positive early-stage breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 Nov 2025 → ongoing

Decision date (initial)

2025-09-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

European Union’s Horizon Europe research and innovation programme, under grant agreement No 10113695

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Safety

To determine whether there is an improvement in the health-related quality of life (HRQoL) following tailored treatment by HER2DX compared with standard of care treatment.

To evaluate whether the strategy of tailoring treatment by HER2DX presents a similar rate of responses than the standard of care treatment.

Secondary objectives 7

1. To evaluate other HRQoL patient-reported outcomes (functional and symptom values) following tailored treatment by HER2DX compared with standard of care treatment.
2. To evaluate whether the strategy of tailoring treatment by HER2DX presents similar efficacy outcomes than the standard of care treatment.
3. To evaluate the association between HER2DX scores and efficacy outcomes
4. To evaluate the safety and tolerability of test guided treatment and their corresponding standard treatment.
5. To evaluate patient experience in control arm compared to those treated using the test and assess whether the inclusion of HER2DX test has an impact on patient experience.
6. Analyze the financial impact of the HER2DX test.
7. To evaluate whether the potential treatment de-escalation following tailored treatment by HER2DX could have impact on the work productivity.

Conditions and MedDRA coding

HER2-positive early breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Signed informed consent must be obtained prior to any trial-specific procedure. Note: Candidate patients in France must be affiliated to a Social Security System (or equivalent).
2. Male/female patients who are at least 18 years of age on the day of signing informed consent.
3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
4. Eligible for taxane, carboplatin, trastuzumab, pertuzumab and T-DM1 therapy
5. Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast untreated and recently diagnosed.
6. Stage at presentation: cT1 cN1-2 or cT2-3 cN0-2 as determined by AJCC staging system, 8th (specifically in accordance with Anatomic Stage group rules).Note: Axillary lymph node status must be assessed by fine needle biopsy or core biopsy. This procedure at screening will be omitted if there is no suspicion for positive axillary lymph node(s) radiographically or if a pathological report of suspicious lymph nodes of the results of a fine needle biopsy or core biopsy is available prior to the screening period.Note: Axillary lymph node status must be assessed by fine needle biopsy or core biopsy. This procedure at screening will be omitted if there is no suspicion for positive axillary lymph node(s) radiographically or if a pathological report of suspicious lymph nodes of the results of a fine needle biopsy or core biopsy is available prior to the screening period.
7. Absence of distant metastasis (i.e., cM0).
8. Patients with multifocal tumors (more than one mass confined to the same quadrant as primary tumor) are eligible provided at least one focus is sampled and locally confirmed as HER2-positive.
9. Patients with multicentric tumors (multiple tumors involving more than one quadrant) are eligible provided all discrete lesions are sampled and locally confirmed as HER2-positive. Note: In patients with multifocal or multicentric breast cancer, the largest lesion should be measured to determine T stage and to perform the HER2DX test.
10. HER2 positivity defined as either of the following: IHC 3+ or HER2 2+/ ISH positive as per most recent ASCOCAP guideline according to the local laboratory as determined on the most recently analyzed tissue sample.
11. ER/PR status determined locally based on pretreatment breast biopsy material according to the most recent ASCO/CAP guidelines.
12. Candidate for neoadjuvant treatment
13. Patient agreement to undergo appropriate surgical management, including axillary lymph node surgery and partial or total mastectomy, after completion of neoadjuvant treatment.
14. Baseline left ventricular ejection fraction (LVEF) ≥ 50% measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans.
15. Availability of pre-treatment tumor tissue sample of FFPE tumor block from primary tumor in the breast for diagnostic HER2DX test. The tumor tissue should be of good quality based on total and viable tumor content and must be evaluated centrally for quality prior to enrolment. Note: A representative archival FFPE specimen of primary tumor in the breast, along with a pathology report documenting HER2 positivity and ER/PR status, will be sent to the central lab. If not available or deficient for quantity or quality, further tumor material may be sent to central lab.
16. Adequate hematologic and end-organ function.
17. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below: - Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period, 6 months after the final dose of doxorubicin, 12 months after the final dose of cyclophosphamide, 6 months after the final dose of paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last. Women must refrain from donating eggs during this same period. - A woman is of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (> 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements. - Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, copper intrauterine devices, hormonal contraceptives that inhibit ovulation, and hormone-releasing intrauterine devices in women with hormone receptor-negative tumors only; the use of hormonal contraceptives and hormone releasing intrauterine devices are prohibited in women with hormone receptor-positive tumors. - The reliability of sexual abstinence should be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
18. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below: - With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 6 months after the final dose of doxorubicin and/or cyclophosphamide, 6 months after the final dose of paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last. Men must refrain from donating sperm during this same period. Male patients are encouraged to seek advice regarding cryoconservation of sperm prior to commencing study treatment because of the possibility of infertility with chemotherapy. - With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 6 months after the final dose of doxorubicin and/or cyclophosphamide, 6 months after the final dose of paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last to avoid exposing the embryo. - The reliability of sexual abstinence should be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

Exclusion criteria 16

1. Stage IV (metastatic) breast cancer.
2. Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the study.
3. Severe infection within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
4. History of significant co-morbidities that, in the judgment of the investigator, may interfere with the conduction of the study, the evaluation of response, or with consent procedure
5. Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 6 months after the final dose of paclitaxel, or 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last. Note: Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study treatment.
6. Persons deprived of their liberty or under protective custody or guardianship
7. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.
8. Known hypersensitivity to any of the excipients of trastuzumab, pertuzumab, carboplatin, T-DM1, docetaxel or paclitaxel.
9. Patients with synchronous bilateral invasive breast cancer.
10. Prior systemic therapy for treatment of breast cancer.
11. Ulcerating or inflammatory breast cancer.
12. Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes
13. Sentinel lymph node procedure or axillary lymph node dissection prior to initiation of neoadjuvant therapy.
14. Patients with a history of previous breast cancer are excluded. Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years are excluded. For patients with a history of other non-breast cancers within 3 years and considered of low risk of recurrence per investigator’s judgment (for example, papillary thyroid cancer treated with surgery), eligibility is to be discussed with Study Sponsor.
15. Cardiopulmonary dysfunction as defined by any of the following prior to randomization: - History of congestive heart failure of any classification. - Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease. - High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block [second degree AV-block Type 2 [Mobitz 2] or third-degree AV-block]). - Significant symptoms (Grade > 1) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia. - Myocardial infarction within 12 months prior to randomization. - Evidence of transmural infarction on ECG. - Requirement for oxygen therapy. - Dyspnea at rest.
16. Patients participating in other clinical trials/ treatments with other IMPs and its relevant metabolites or previous therapies, whose toxicity (may) overlap with that of the IMP and its relevant metabolites within five times the halflife of the drug/metabolites (whichever is longer).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The study will evaluate superiority in quality of life using i) the global health status (GHS) scale from the EORTC QLQ-C30 questionnaire version 3.0 and ii) the score from the FACIT Fatigue Scale (Version 4). Dual primary quality of life endpoints: • The GHS scale is based on two 7-point questions (from very poor to excellent, items 29-30 from EORTC QLQ-C30 questionnaire). • The score from the FACIT Fatigue Scale is based on 13-item questionnaire (from 0 to 4). The total score ranges from 0 t

Secondary endpoints 7

1. Change from baseline in all other functional and symptom scales from the EORTC QLQ-C30 questionnaire. Change from baseline to surgery in the score of the EuroQol-5D.
2. The residual cancer burden (RCB), when available. RCB is defined as classes 0, 1, 2 and 3, according to the MD Anderson Cancer Center recommendations by local evaluation. The invasive disease-free survival (iDFS), distant metastasis free survival (DMFS), recurrence-free interval (RFI) and event-free survival (EFS) of patients.
3. PCR rates according to the predefined HER2DX pCR score i) as a continuous variable and ii) as group categories. The RCB (when available) according to HER2DX pCR score as a continuous variable and as group categories. RCB is defined as classes 0, 1, 2 and 3, according to the MD Anderson Cancer Center recommendations by local evaluation in both treatment arms according to HER2DX pCR score in continuous variable and risk group.The iDFS, DMFS, RFI and EFS of patients according to HER2DX risk scor
4. Incidence, duration, and severity of AEs assessed by the NCI Common Terminology for Classification of AEs (CTCAE) version 5, including dose reductions, delays, and treatment discontinuations. Percentage of amenorrhea one year after finishing the neo/adjuvant treatment in premenopausal women without LHRH treatment.
5. The following dimensions of experience will be evaluated: Team accessibility, Communication, Information from care providers, Care continuum coordination, respect and courtesy, secondary effects management, shared decision making, language barriers and overall care perception, using the CAHPS cancer care survey (AHQR).
6. Health economic evaluation to compare the cost-effectiveness in patients with and without HER2DX test information, not only direct cost for hospitals/public health system, but also indirect cost for public system.
7. The Work Productivity and Activity Impairment Questionnaire (WPAI-GH).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 10

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Sponsor organisation

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Address

Calle Rosellon 149-153

City

Barcelona

Postcode

08036

Country

Spain

Scientific contact point

Organisation

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Contact name

Susana Belmonte Gargallo

Public contact point

Organisation

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Contact name

Susana Belmonte Gargallo

Locations

4 EU/EEA countries · 31 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 40 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications