PATRITUMAB DERUXTECAN for Hormone receptor-positive (HR+) HER2-negative high-risk early breast cancer

Inclusion criteria

• {"criterion_text":"- Signed ICF"}
• {"criterion_text":"- Adequate hematologic and end-organ function"}
• {"criterion_text":"- willing and able to comply with trial procedures."}
• {"criterion_text":"- Women of childbearing potential must have confirmed negative serum pregnancy test"}
• {"criterion_text":"- Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the time of final study drug administration."}
• {"criterion_text":"- Women of CBP must be willing to use highly effective methods of contraception."}
• {"criterion_text":"- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception and fetal protection for the duration of neoadjuvant treatment phase and after the last dose of treatment according to protocol."}
• {"criterion_text":"- Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and for at least 4 months after the final study drug administration."}
• {"criterion_text":"- Postmenopausal or pre-menopausal"}
• {"criterion_text":"- Patients must have the ability to swallow oral medication."}
• {"criterion_text":"- Baseline LVEF ≥ 50%"}
• {"criterion_text":"- Male/female . At least 18 years old"}
• {"criterion_text":"- Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast untreated and recently diagnosed, Stage II to stage IIIB breast cancer, Absence of distant metastasis. At least 1 lesion ≥ 10 mm by MRI"}
• {"criterion_text":"- ER-positive and/or PgR-positive and HER2-negative tumor"}
• {"criterion_text":"- Ki67 IHC % ≥ 20% locally assessed and/or high genomic risk (defined by gene signature): Oncotype DX® RS ≥ 26, Mammaprint® = Risk of Recurrence High Endopredict® = High Risk or Prosigna® ROR ≥ 60."}
• {"criterion_text":"- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1."}
• {"criterion_text":"- Breast cancer eligible for primary surgery."}
• {"criterion_text":"- Availability of pre-treatment tumor tissue sample of FFPE tumor block from primary tumor for biomarker analysis."}
• {"criterion_text":"- Eligible for neoadjuvant chemotherapy"}

Exclusion criteria

• {"criterion_text":"- Metastatic (Stage IV) breast cancer."}
• {"criterion_text":"- Patients with a history of any malignancy are ineligible (some exception detailed in protocol)"}
• {"criterion_text":"- Current severe, uncontrolled systemic disease or other factors which in the Investigator's opinion makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol"}
• {"criterion_text":"- Concurrent, serious, uncontrolled infections or current known infection with HIV or active hepatitis B and/or hepatitis C"}
• {"criterion_text":"- 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 ICF."}
• {"criterion_text":"- Known hypersensitivity to either the drug substance components or inactive ingredients in the drug product or history of severe hypersensitivity reactions to other monoclonal antibodies."}
• {"criterion_text":"- History of exposure to cumulative anthracycline"}
• {"criterion_text":"- Any history of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during screening."}
• {"criterion_text":"- Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement."}
• {"criterion_text":"- Has unresolved toxicities from previous anticancer therapy"}
• {"criterion_text":"- Non-eligible for taxanes therapy."}
• {"criterion_text":"- Bilateral invasive breast cancer."}
• {"criterion_text":"- Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1."}
• {"criterion_text":"- Evidence of any leptomeningeal disease."}
• {"criterion_text":"- Has clinically significant corneal disease."}
• {"criterion_text":"- Female subject who is pregnant or breastfeeding or intends to become pregnant during the study."}
• {"criterion_text":"- Subjects who are currently receiving chloroquine or hydroxychloroquine. A washout period of > 14 days is required prior to randomization or Cycle 1 Day 1"}
• {"criterion_text":"- Any treatment for the currently diagnosed BC prior to enrollment."}
• {"criterion_text":"- Patients in whom a primary tumor excisional biopsy was performed"}
• {"criterion_text":"- Prior treatment with a HER3 antibody, topoisomerase I inhibitor, with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g., DS-8201) and with a govitecan derivative (e.g., IMMU- 132)."}
• {"criterion_text":"- Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:"}
• {"criterion_text":"- Medical history of clinically significant lung diseases (e.g., interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or who are suspected to have these diseases by imaging at screening period."}
• {"criterion_text":"- Major surgical procedure or significant traumatic injury within 28 days prior to randomization."}
• {"criterion_text":"- Assessment by the investigator to be unable or unwilling to comply with the requirements of the protocol."}

Primary endpoints

• {"endpoint_text":"- Rate of pCRBL (ypT0/is ypN0) at surgery, defined as the complete absence of invasive carcinoma in the breast and axillary lymph nodes on histological examination","definition_or_measurement_approach":"Complete absence of invasive carcinoma in the breast and axillary lymph nodes on histological examination (pCRBL: ypT0/is ypN0) assessed at surgery."}

Secondary endpoints

• {"endpoint_text":"- Rate of Residual cancer burden (RCB) category status (0, I, II, III) assessed by a local pathologist at surgery according to the MD Anderson Cancer Center recommendations.","definition_or_measurement_approach":"RCB category (0, I, II, III) assessed by local pathologist at surgery per MD Anderson Cancer Center recommendations."}
• {"endpoint_text":"- pCRB defined as the complete absence of invasive carcinoma in the breast on histological examination after treatment, irrespective of in situ carcinoma in the breast.","definition_or_measurement_approach":"Absence of invasive carcinoma in the breast on histology after treatment (irrespective of in situ carcinoma)."}
• {"endpoint_text":"- Tumor overall objective response rate (ORR), defined as the proportion of subjects with a Partial Responses (PR) or a Complete Responses (CR) according to RECIST v1.1, as per Investigator's assessments by breast MRI before treatment and pre-surgery.","definition_or_measurement_approach":"ORR = proportion of subjects with PR or CR per RECIST v1.1 by investigator assessment using breast MRI pre-treatment and pre-surgery."}
• {"endpoint_text":"- iDFS rate at 3 years follow-up","definition_or_measurement_approach":"Invasive disease-free survival (iDFS) rate measured at 3 years follow-up."}
• {"endpoint_text":"- iDFS rate at 5 years follow-up","definition_or_measurement_approach":"Invasive disease-free survival (iDFS) rate measured at 5 years follow-up."}
• {"endpoint_text":"- Change in CelTIL score from baseline to C2D1.","definition_or_measurement_approach":"Change in CelTIL biomarker score from baseline to Cycle 2 Day 1."}
• {"endpoint_text":"- The Correlation of CelTIL changes from baseline to C2D1 with: pCR, RCB, ORR and iDFS.","definition_or_measurement_approach":"Correlation analyses between CelTIL change (baseline to C2D1) and pCR, RCB, ORR, and iDFS."}
• {"endpoint_text":"- The correlation of pCR with both HER3 receptor expression levels by IHC at baseline and ERBB3 mRNA expression level by gene expression at baseline.","definition_or_measurement_approach":"Correlation of pCR with baseline HER3 IHC expression and baseline ERBB3 mRNA expression."}
• {"endpoint_text":"- The correlation of pCR with changes of HER3 receptor expression levels by IHC and ERBB3 mRNA expression level by gene expression between baseline and C2D1.","definition_or_measurement_approach":"Correlation of pCR with changes in HER3 IHC expression and ERBB3 mRNA expression between baseline and C2D1."}
• {"endpoint_text":"- Change in Ki67 IHC from baseline to C2D1.","definition_or_measurement_approach":"Change in Ki67 IHC percentage from baseline to Cycle 2 Day 1."}
• {"endpoint_text":"- and correlation of Ki67 IHC changes from baseline to C2D1 with: pCR, RCB, ORR and iDFS.","definition_or_measurement_approach":"Correlation analyses between Ki67 IHC change (baseline to C2D1) and pCR, RCB, ORR, and iDFS."}
• {"endpoint_text":"- Type, incidence, severity (as graded by the NCI CTCAE v. 5.0), seriousness, moment of onset, duration and attribution to the study medications of TEAEs, AESI and any laboratory abnormalities.","definition_or_measurement_approach":"Safety assessments: TEAEs, AESIs and laboratory abnormalities characterised by type, incidence, severity (NCI CTCAE v5.0), seriousness, onset, duration and attribution to study medications."}
• {"endpoint_text":"- Change from baseline in EORTC QLQ-C30 and EORTC QLQ BR23 scores.","definition_or_measurement_approach":"Change from baseline in health-related quality of life measured by EORTC QLQ-C30 and EORTC QLQ-BR23 instruments."}

Spain

Earliest CTIS Part Ii Submission Date

19-12-2023

Latest Decision Or Authorization Date

18-01-2024

Processing Time Days

30

Number Of Sites

25

Number Of Participants

120

Primary sponsor

Full Name

Solti Group

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Third parties

• {"country":"","full_name":"Daiichi Sankyo","duties_or_roles":"Source of monetary support","organisation_type":""}