TRASTUZUMAB DERUXTECAN for High-risk HER2-positive breast cancer

Inclusion criteria

• {"criterion_text":"- Sign and date the tissue screening and main ICFs, prior to the start of any study-specific qualification procedures.\n- Known hormone receptor status, per local laboratory assessment, as defined by ASCO-CAP guidelines (≥1%): HR-positive status defined by either positive estrogen receptor (ER) or positive progesterone receptor (PR) status. HR-negative status defined by both known negative ER and known negative PR.\n- Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days prior to randomization.\n- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n- Has adequate organ function within 14 days before randomization as defined in the protocol.\n- Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 4 months for males and 7 months for females after the last dose of study drug. See protocol for full details\n- Male subjects must not freeze or donate sperm starting at randomization and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrolment in this study.\n- Female subjects must not donate, or retrieve for their own use, ova from the time of randomization and throughout the study treatment period, and for at least 7 months after the final study drug administration. They should refrain from breastfeeding throughout this time. Preservation of ova may be considered prior to randomization in this study.\n- Adults ≥18 y old. (Please follow local regulatory requirements if the legal age of consent for study participation is >18 y old).\n- HER2-positive breast cancer, meeting all of the criteria listed in the protocol (see protocol for full details).\n- Histologically confirmed invasive breast carcinoma at time of disease presentation. Subjects with inflammatory breast cancer are allowed provided all eligibility criteria are met.\n- Clinical stage at disease presentation of T1-4, N0-3, M0 prior to neoadjuvant therapy (Note: Patients presenting with T1N0 tumors will not be eligible).\n- Pathologic evidence of residual invasive carcinoma in the breast and/or axillary lymph nodes following completion of neoadjuvant therapy meeting one of the high risk criteria described in detail in the protocol.\n- Completion of neoadjuvant systemic therapy, including taxane-based chemotherapy and HER2-directed treatment prior to surgery\n- Adequate excision as confirmed per medical records: surgical removal of all clinically evident disease in the breast and axillary lymph nodes (see Section 8.1.2).\n- An interval of no more than 12 weeks between the date of last surgery and the date of randomization."}

Exclusion criteria

• {"criterion_text":"- Stage IV (metastatic) breast cancer.\n- Any autoimmune, connective tissue or inflammatory disorders (eg, Rheumatoid arthritis, Sjogren's, sarcoidosis, etc...) where there is documented, or a suspicion of pulmonary involvement, or pneumonectomy at the time of screening\n- Uncontrolled or significant cardiovascular disease, including: Medical history of myocardial infarction within 6 months before randomization, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to randomization.\n- Has a corrected QT interval per Fridericia's formula (QTcF) prolongation to > 470 msec (females) or > 450 msec (males) based on screening 12-lead electrocardiogram (ECG).\n- History of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.\n- History of severe hypersensitivity reactions to other monoclonal antibodies (MAb).\n- Inadequate washout period before Randomization/Cycle 1 Day 1, as defined in the protocol.\n- Substance abuse or 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.\n- Social, familial, or geographical factors that would interfere with study participation or follow-up.\n- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.\n- Active primary immunodeficiency, known uncontrolled active HIV infection or active hepatitis B or C infection.\n- History of any prior (ipsi- or contralateral) breast cancer except lobular carcinoma in situ (LCIS).\n- Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline.\n- Is pregnant or breastfeeding or planning to become pregnant.\n- Has history of receiving live, attenuated vaccine (mRNA and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study intervention\n- Evidence of clinically evident gross residual or recurrent disease following neoadjuvant therapy and surgery (see Section 8.1.2.1).\n- An overall response of progressive disease according to the investigator at the conclusion of preoperative systemic therapy\n- Prior treatment with T-DXd, T-DM1 or other anti-HER2 ADC or prior enrollment in any clinical trial with T-DXd (regardless of treatment arm).\n- History of exposure to the following cumulative doses of anthracyclines (see protocol for full details).\n- History of other malignancy within the last 5 years except for appropriately treated carcinoma in situ (CIS) of the cervix, nonmelanoma skin carcinoma, Stage I melanoma skin carcinoma, Stage I uterine cancer, or other appropriately treated non-breast malignancies with an outcome similar to those mentioned above.\n- History of (noninfectious) ILD/pneumonitis that required steroids or has ILD/pneumonitis noted on computed tomography (CT) scan of the chest at Screening (asymptomatic interstitial changes confined to recent radiation therapy fields are not excluded).\n- Known pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within three months prior to randomization, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, etc.)."}

Primary endpoints

• {"endpoint_text":"- IDFS is defined as the time from randomization until the first occurrence of ipsilateral locoregional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause.","definition_or_measurement_approach":"IDFS is defined as the time from randomization until the first occurrence of ipsilateral locoregional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause."}
• {"endpoint_text":"- IDFS will be determined based on disease recurrence per Investigator assessment based on all available clinical assessments.","definition_or_measurement_approach":"Determined based on disease recurrence per Investigator assessment using all available clinical assessments."}

Secondary endpoints

• {"endpoint_text":"- DFS is defined as the time between randomization and the date of the first occurrence of an IDFS event including second primary non-breast cancer event or contralateral or ipsilateral DCIS. DFS will be determined based on disease recurrence per Investigator assessment.","definition_or_measurement_approach":"Time from randomization to first occurrence of an IDFS event including second primary non-breast cancer or contralateral/ipsilateral DCIS; determined by Investigator assessment."}
• {"endpoint_text":"- OS is defined as the time from randomization to death due to any cause.","definition_or_measurement_approach":"Time from randomization to death from any cause."}
• {"endpoint_text":"- DRFI is defined as the time between randomization and the date of distant breast cancer recurrence. DRFI will be determined based on disease recurrence per Investigator assessment.","definition_or_measurement_approach":"Time from randomization to date of distant breast cancer recurrence; determined by Investigator assessment."}
• {"endpoint_text":"- BMFI is defined as time from randomization to documentation of involvement of the CNS by metastatic cancer including parenchymal brain and spinal cord metastases as well as leptomeningeal carcinomatosis. BMFI will be determined based on disease recurrence per Investigator assessment.","definition_or_measurement_approach":"Time from randomization to documentation of CNS involvement by metastatic cancer (brain/spinal cord metastases or leptomeningeal carcinomatosis); determined by Investigator assessment."}
• {"endpoint_text":"- AEs including SAEs, TEAEs, and AESIs Physical examination findings, ECOG PS, vital sign measurements, standard clinical laboratory parameters, ECG parameters, ECHO/MUGA findings, and CT scans","definition_or_measurement_approach":"Safety endpoints include adverse events (SAEs, TEAEs, AESIs) and clinical/laboratory/diagnostic assessments (physical exam, ECOG PS, vitals, labs, ECG, ECHO/MUGA, CT scans)."}
• {"endpoint_text":"- Serum concentrations of T-DXd, total anti HER2 antibody, and MAAA 1181a in the PK sampling cohort","definition_or_measurement_approach":"Pharmacokinetic sampling to determine serum concentrations of T-DXd, total anti-HER2 antibody, and MAAA 1181a in the PK cohort."}
• {"endpoint_text":"- Percentage of subjects who are positive for ADAs at baseline, and postbaseline and treatment-emergent ADA positive. Titer and NAb will be determined for positive ADA samples.","definition_or_measurement_approach":"Immunogenicity: percent ADA-positive at baseline/postbaseline and treatment-emergent ADA; titers and neutralizing antibodies (NAb) measured for ADA-positive samples."}

Spain

Latest Decision Or Authorization Date

10-07-2024

Number Of Participants

208

Italy

Latest Decision Or Authorization Date

29-07-2024

Number Of Participants

158

Ireland

Latest Decision Or Authorization Date

10-07-2024

Number Of Participants

47

Germany

Latest Decision Or Authorization Date

19-07-2024

Number Of Participants

210

Romania

Latest Decision Or Authorization Date

07-08-2024

Number Of Participants

63

Poland

Latest Decision Or Authorization Date

04-08-2024

Number Of Participants

154

Belgium

Latest Decision Or Authorization Date

15-07-2024

Number Of Participants

35

Czechia

Latest Decision Or Authorization Date

11-07-2024

Number Of Participants

12

Denmark

Latest Decision Or Authorization Date

12-07-2024

Number Of Participants

20

Greece

Latest Decision Or Authorization Date

22-07-2024

Number Of Participants

22

Netherlands

Latest Decision Or Authorization Date

10-07-2024

Number Of Participants

18

France

Latest Decision Or Authorization Date

11-07-2024

Number Of Participants

143

Portugal

Latest Decision Or Authorization Date

12-07-2024

Number Of Participants

34

Primary sponsor

Full Name

Daiichi Sankyo Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Syneos Health Netherlands B.V.

Responsibilities

1|10|12|13|2|5|6|7|8|9

Name

Syneos Health Hellas Single Member S.A.

Responsibilities

1|10|12|13|2|5|6|7|8|9

Name

Syneos Health Romania S.R.L.

Responsibilities

1|10|12|13|2|5|6|7|8|9

Third parties

• {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"1|10|12|13|2|5|6|7|8|9","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Syneos Health Hellas Single Member S.A.","duties_or_roles":"1|10|12|13|2|5|6|7|8|9","organisation_type":"Pharmaceutical company"}
• {"country":"Romania","full_name":"Syneos Health Romania S.R.L.","duties_or_roles":"1|10|12|13|2|5|6|7|8|9","organisation_type":"Pharmaceutical company"}