Therapy with an antibody-drug conjugate in patients with early HER2-negative breast cancer and high risk of relapse after neoadjuvant chemotherapy in primary HER2-negative breast cancer patients

Phase 1

• Conditions: HER2-negative breast cancer patients with high relapse risk after standard neoadjuvant treatment; MedDRA version: 21.1Level: PTClassification code 10057654Term: Breast cancer femaleSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10061020Term: Breast cancer maleSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10006198Term: Breast cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10006199Term: Breast cancer stage ISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10006200Term: Breast cancer stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10006201Term: Breast cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-004100-35-AT
• Lead Sponsor: GBG Forschungs GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-01-31
• Last Update Posted: 15 July 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 1332

Inclusion Criteria

Patients with residual invasive disease after neoadjuvant chemotherapy at high risk of recurrence defined by either:
- For HR-negative: any residual invasive disease > ypT1mi
- For HR-positive disease: a CPS+EG score = 3 or CPS+EG score 2 and ypN+ using local ER and grade assessed on core biopsies taken before start of neoadjuvant treatment.
-Patients must have received neoadjuvant taxane-based chemotherapy for 16 weeks (anthracyclines are permitted). This period must include 6 weeks of a taxane containing neoadjuvant chemotherapy (exception: for patients with progressive disease that occurred after at least 6 weeks of taxane-containing neoadjuvant chemotherapy, a total treatment period of less than 16 weeks is also eligible).
-An interval of less than 16 weeks since the date of final surgery or less than 10 weeks from completing radiotherapy (whichever occurs last) and the date of randomization is required
-Radiotherapy should be delivered before the start of study treatment.
Radiotherapy to the breast is indicated in all patients with breast conserving surgery and to the chest
wall and lymph nodes according to local guidelines as well as in all patients with cT3/4 or ypN+ disease treated by mastectomy.
-Immune checkpoint inhibitor / immunotherapy during neoadjuvant therapy is allowed until the completion of radiotherapy
-Patients with known gBRCA1/2 mutation without indication to adjuvant olaparib therapy are allowed to participate in the trial.
-Willingness and ability to provide archived formalin fixed paraffin embedded tissue (FFPE) block from surgery after neoadjuvant chemotherapy and from core biopsy before start of neoadjuvant chemotherapy, which will be used for centralized prospective confirmation of HR status, HER2status, Ki-67 and tumor-infiltrating lymphocytes (TILs) and for retrospective exploratory correlation between genes, proteins, and mRNAs relevant to sensitivity/resistance to the investigational agents. For patients with bilateral carcinoma, FFPE blocks from both sides have to be provided for central testing.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1332
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1332

Exclusion Criteria

-Patients with definitive clinical or radiologic evidence of stage IV cancer (metastatic disease) are not eligible.
-Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study, including Gilbert´s disease, Crigler-Najjar Syndrom, known hepatitis B, hepatitis C, known HIV positivity or known autoimmune disease (other than diabetes, vitiligo, or stable thyroid disease)
-Patients with known gBRCA1/2 mutation and indicated or planned
adjuvant olaparib therapy if available
-Known or suspected congestive heart failure (>NYHA I) and/or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of prior infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP >150/90 mmHg under treatment with at maximum three antihypertensive drugs), rhythm abnormalities requiring permanent treatment (excluding chronic atrial fibrillation not requiring a pacemaker), clinically significant valvular heart disease, supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; conduction abnormality requiring a pacemaker.
-Known allergic reactions to irinotecan.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified