DATOPOTAMAB DERUXTECAN for Hormone receptor-positive breast cancer | Locally advanced breast cancer | Metastatic breast cancer

Inclusion criteria

• {"criterion_text":"- Inoperable or metastatic HR-positive, HER2 IHC 0 breast cancer (per ASCO/CAP guidelines, on local laboratory results); ie, is documented as HR-positive (either ER and/or PgR positive [ER or PgR ≥ 1%]) and HER2 IHC 0 (defined as no staining or incomplete and faint/barely perceptible membrane staining in ≤ 10% of tumour cells).\n- Progressed on and/or not suitable for further endocrine-based therapy per investigator assessment.\n- ECOG performance status of 0 or 1, with no deterioration over the previous 2 weeks prior to the first dose of study intervention.\n- Minimum life expectancy of 12 weeks at screening.\n- Provision of acceptable tumour sample prior to the first dose of study intervention or retrospectively\n- Participants must have measurable disease as per RECIST 1.1 or evaluable disease. Lesions that will be subject to mandatory biopsy before, during, and after the dosing cannot be considered as TLs as per RECIST requirements.\n- Adequate bone marrow reserve and organ function within 7 days before the first dose of study intervention.\n- Not a candidate for T-DXd, defined as: (a) Participants whose tumours are HER2 IHC 0 with no membrane staining observed (b) Participants whose tumours are HER2-ultralow (IHC 0 with membrane staining that is incomplete and is faint/barely perceptible and in ≤ 10% of tumour cells) and have: (i) comorbidities precluding treatment with T-DXd, or (ii) no access to T-DXd (participant’s country has no regulatory access or no reimbursement at the time of screening)."}

Exclusion criteria

• {"criterion_text":"- As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases and significant cardiac or psychological conditions), history of allogenic organ transplant, and/or substance abuse which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.\n- Severe pulmonary function compromise\n- History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer (basal cell carcinoma of the skin or squamous cell carcinoma of the skin) and curatively treated in situ disease.\n- Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved to Grade ≤ 1 or baseline. Note: participants may be enrolled with some chronic, stable Grade 2 toxicities (defined as no worsening to Grade > 2 for at least 3 months prior to the first dose of study intervention and managed with SoC treatment) which the investigator deems related to previous anticancer therapy\n- Spinal cord compression or brain metastases (unless asymptomatic, stable, and not requiring treatment with corticosteroids or anticonvulsants for at least 2 weeks prior to the first dose of study intervention). Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants must have recovered from the acute toxic effect of radiotherapy (eg, dizziness and signs of increased intracranial pressure). A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and the first dose of study intervention. A minimum of 3 days must have elapsed between the end of corticosteroid therapy for CNS metastatic disease and the first dose of study intervention.\n- Leptomeningeal carcinomatosis or metastasis.\n- Active or uncontrolled hepatitis B or C virus infection\n- Known HIV infection that is not well controlled\n- Clinically significant corneal disease\n- History of non-infectious ILD/pneumonitis, including radiation pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening"}

Primary endpoints

• {"endpoint_text":"- PFS is defined as time from date of first dose of study intervention until progression per RECIST 1.1 as assessed by the investigator or death due to any cause. The analysis will include all dosed participants. All events will be included, regardless of whether the participant withdraws from therapy, receives another anticancer therapy, or experiences clinical progression prior to RECIST 1.1.","definition_or_measurement_approach":"PFS measured as time from first dose to progression per RECIST 1.1 as assessed by investigator or death from any cause; analysis will include all dosed participants and all events regardless of subsequent therapies or withdrawal."}

Secondary endpoints

• {"endpoint_text":"- Proportion of participants with oral mucositis/stomatitis . Proportion of participants with ocular events. Proportion of participants with Grade 3 or higher AEs possibly related to Dato-DXd treatment (Grade ≥ 3 treatment-related AEs) according to NCI CTCAE 5.0.","definition_or_measurement_approach":"Safety endpoints measured as proportions of participants experiencing oral mucositis/stomatitis, ocular events, and Grade ≥3 treatment-related AEs per NCI CTCAE v5.0."}
• {"endpoint_text":"- CBR at 24 weeks is defined as the percentage of participants who have a confirmed CR or PR or who have SD per RECIST 1.1 as assessed by the investigator and derived from the raw tumour data for at least 24 weeks after date of first dose.","definition_or_measurement_approach":"CBR at 24 weeks = % participants with confirmed CR or PR or SD per RECIST 1.1 for at least 24 weeks after first dose, assessed by investigator from raw tumour data."}
• {"endpoint_text":"- ORR is defined as the proportion of participants with measurable disease at baseline who have a confirmed CR or confirmed PR, as assessed by the investigator and derived from raw tumour data per RECIST 1.1. The analysis will include all dosed participants with measurable disease at baseline.","definition_or_measurement_approach":"ORR = proportion of participants with measurable disease at baseline who achieve confirmed CR or PR per RECIST 1.1, assessed by investigator from raw tumour data; analysis includes all dosed participants with measurable disease at baseline."}
• {"endpoint_text":"- DoR will be defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 as assessed by the investigator or death due to any cause. The analysis will include all dosed participants who have a confirmed response.","definition_or_measurement_approach":"Duration of Response = time from first documented confirmed response to documented progression per RECIST 1.1 or death; includes all dosed participants with confirmed response."}
• {"endpoint_text":"- OS defined as the time from the date of the first dose of study intervention until the date of death due to any cause. The analysis will include all dosed participants. All deaths will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy. The measure of interest is the OS rate at 6 months.","definition_or_measurement_approach":"Overall Survival = time from first dose to death from any cause; analysis includes all dosed participants; primary measure of interest is OS rate at 6 months."}

Spain

Earliest CTIS Part Ii Submission Date

30-10-2025

Latest Decision Or Authorization Date

07-11-2025

Processing Time Days

8

Number Of Sites

9

Number Of Participants

20

Italy

Earliest CTIS Part Ii Submission Date

06-10-2025

Latest Decision Or Authorization Date

05-11-2025

Processing Time Days

30

Number Of Sites

6

Number Of Participants

16

France

Earliest CTIS Part Ii Submission Date

29-09-2025

Latest Decision Or Authorization Date

10-11-2025

Processing Time Days

42

Number Of Sites

5

Number Of Participants

14

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

Almac Clinical Services (Ireland) Limited

Responsibilities

code:15 (drug Mestruction)

Name

PPD Development LP

Responsibilities

code:4

Name

Fortrea Inc.

Responsibilities

code:1, code:2, code:5, code:6, code:8

Name

Perceptive Informatics Inc.

Responsibilities

code:3

Name

Medidata Solutions Inc.

Responsibilities

code:7

Name

Clario Medical Imaging Inc.

Responsibilities

code:15 (ILD adjudication)

Third parties

• {"country":"Ireland","full_name":"Almac Clinical Services (Ireland) Limited","duties_or_roles":"code:15 (drug Mestruction)","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Clario Medical Imaging Inc.","duties_or_roles":"code:15 (ILD adjudication)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scarritt Group Inc.","duties_or_roles":"code:15 (Patient expenses reimbursement)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"code:3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"code:1, code:2, code:5, code:6, code:8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code:7","organisation_type":"Non-Pharmaceutical company"}