DATOPOTAMAB DERUXTECAN for Triple-negative breast cancer

Inclusion criteria

• {"criterion_text":"-Histologically or cytologically documented locally recurrent inoperable, which cannot be treated with curative intent, or metastatic TNBC, as defined by the the ASCO-CAP guidelines"}
• {"criterion_text":"-ECOG PS 0 or 1"}
• {"criterion_text":"-Participants are expected to provide a FFPE tumour sample collected from a locally recurrent inoperable or metastatic tumour (either de novo metastatic or recurrent metastatic, excluding bone metastases). Alternatively, an archival FFPE tumour sample can be submitted. This archival sample may come from early-stage TNBC; however, it must have been collected ≤ 3 years prior to the participant signing informed consent (screening start)."}
• {"criterion_text":"-PD-L1 positive TNBC based on results from an appropriately validated investigational PD-L1 (22C3) assay (CPS ≥ 10) from a sponsor designated central laboratory"}
• {"criterion_text":"-No prior chemotherapy or other systemic anti-cancer therapy for metastatic or locally recurrent inoperable breast cancer. Patients with recurrent disease will be eligible if they have completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months have elapsed between completion of treatment with curative intent and the first documented inoperable local recurrence or distant recurrence."}
• {"criterion_text":"-Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin)"}
• {"criterion_text":"-Measurable disease as per RECIST 1.1"}
• {"criterion_text":"-Adequate bone marrow reserve and organ function"}
• {"criterion_text":"-Male and female participants of childbearing potential must agree to use protocol-specified method(s) of contraception"}

Exclusion criteria

• {"criterion_text":"-As judged by the investigator, severe or uncontrolled systemic diseases, uncontrolled hypertension, serious gastrointestinal conditions associated with diarrhoea, chronic diverticulitis or previous complicated diverticulitis, history of allogeneic organ transplant, and active bleeding diseases, ongoing or active infection, significant cardiac conditions, substance abuse, psychiatric illness/social situation, or psychological conditions."}
• {"criterion_text":"-Clinically significant corneal disease"}
• {"criterion_text":"-Active or prior documented autoimmune or inflammatory disorders"}
• {"criterion_text":"-Prior exposure to any treatment including ADC containing a chemotherapeutic agent targeting topoisomerase I and TROP2-targeted therapy"}
• {"criterion_text":"-Any concurrent anti-cancer treatment"}
• {"criterion_text":"-Participants with a known severe hypersensitivity to PD-1/PD-L1 inhibitors or Dato-DXd"}
• {"criterion_text":"-Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant"}
• {"criterion_text":"-History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before Cycle 1 Day 1 and of low potential risk for recurrence."}
• {"criterion_text":"-Neoplastic spinal cord compression or active brain metastases, leptomeningeal carcinomatosis or history of leptomeningeal carcinomatosis. Participants with a history of previously treated neoplastic spinal cord compression or treated, clinically inactive brain metastases that are no longer symptomatic, who require no treatment with corticosteroids or anticonvulsants, may be included in the study if they have recovered from acute toxic effects of radiotherapy."}
• {"criterion_text":"-Uncontrolled infection requiring IV antibiotics, antivirals or antifungals"}
• {"criterion_text":"-Active or uncontrolled hepatitis B or C virus infection"}
• {"criterion_text":"-Known HIV infection that is not well controlled"}
• {"criterion_text":"-Uncontrolled or significant cardiac disease"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Clinically severe pulmonary function compromise."}

Primary endpoints

• {"endpoint_text":"-PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.","definition_or_measurement_approach":"PFS defined as time from randomisation until progression per RECIST 1.1 assessed by BICR, or death due to any cause."}
• {"endpoint_text":"-The comparison will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anticancer therapy or clinically progresses prior to RECIST 1.1 progression.","definition_or_measurement_approach":"Analysis includes all randomised participants as randomised (intention-to-treat), regardless of subsequent therapy or withdrawal."}
• {"endpoint_text":"-However, if the participant progresses or dies immediately after 2 or more consecutive missed visits, the participant will be censored at the time of the latest evaluable assessment prior to the 2 missed visits. The measure of interest is the HR of PFS.","definition_or_measurement_approach":"Censoring rule: participants with progression or death immediately after ≥2 consecutive missed visits will be censored at the last evaluable assessment prior to the missed visits. The primary measure is hazard ratio (HR) for PFS."}

Secondary endpoints

• {"endpoint_text":"-Overall Survival (OS): OS is defined as the time from the date of randomisation until death due to any cause.","definition_or_measurement_approach":"OS defined as time from randomisation until death due to any cause."}
• {"endpoint_text":"-Objective Response Rate (ORR): Objective response rate is defined as the proportion of participants who have a CR or PR, as determined by the BICR/Investigator assessment, per RECIST 1.1.","definition_or_measurement_approach":"ORR = proportion with CR or PR per RECIST 1.1 by BICR/Investigator assessment."}
• {"endpoint_text":"-Duration of Response (DoR): Duration of response is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1, as assessed by BICR/Investigator assessment or death due to any cause.","definition_or_measurement_approach":"DoR = time from first documented response to documented progression per RECIST 1.1 (BICR/Investigator) or death."}
• {"endpoint_text":"-Progression-Free Survival (PFS) by Investigator assessment: PFS by Investigator assessment will be defined as the time from the date of randomization until the date of PD per RECIST 1.1 by Investigator assessment or death due to any cause","definition_or_measurement_approach":"Investigator-assessed PFS defined as time from randomisation to PD per RECIST 1.1 by investigator assessment or death."}
• {"endpoint_text":"-Clinical benefit rate (CBR) at 24 weeks: is defined as the percentage of participants who have a CR or PR or who have SD, per RECIST 1.1, as assessed by BICR/per investigator assessment and derived from the raw tumour data for at least 23 weeks after randomisation.","definition_or_measurement_approach":"CBR at 24 weeks = percent with CR, PR or SD per RECIST 1.1 assessed by BICR/investigator and derived from tumour data for ≥23 weeks post-randomisation."}
• {"endpoint_text":"-Clinical Outcome Assessments: The secondary PRO endpoints include: TTD in breast symptoms as measured by breast symptoms scale from EORTC IL116, TTD in arm symptoms as measured by arm symptoms scale from EORTC IL116, TTD in pain as measured by the pain scale from EORTC IL199, TTD in physical functioning as measured by the physical functioning scale from the PROMIS Short Form v2.0 – Physical Function 8c, TTD in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172.","definition_or_measurement_approach":"PRO endpoints (TTD) measured using specified EORTC and PROMIS scales (EORTC IL116, IL199, PROMIS Short Form v2.0 Physical Function 8c, EORTC IL172)."}
• {"endpoint_text":"-Time to First Subsequent Therapy (TFST): Time to first subsequent therapy is defined as the time from randomization until the start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause.","definition_or_measurement_approach":"TFST = time from randomisation to start date of first subsequent anticancer therapy after discontinuation of randomized treatment, or death."}
• {"endpoint_text":"-Time to Second Subsequent Therapy (TSST): Time to second subsequent therapy is defined as the time from randomization to until the start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause.","definition_or_measurement_approach":"TSST = time from randomisation to start date of second subsequent anticancer therapy after discontinuation of first subsequent therapy, or death."}
• {"endpoint_text":"-Time from randomization to second progression or death (PFS2): Time to second progression of death will be defined as the time from the randomization to the earliest progression event (following the initial progression), subsequent to first subsequent therapy, or death. The date of second progression will be recorded by the Investigator in the eCRF and defined according to local standard clinical practice based on radiological or clinical progression.","definition_or_measurement_approach":"PFS2 = time from randomisation to earliest second progression event (after initial progression) following first subsequent therapy, or death; date recorded by Investigator in eCRF per local clinical practice."}
• {"endpoint_text":"-Pharmacokinetics of dato-DXd in combination with durvalumab","definition_or_measurement_approach":"PK of Dato-DXd when combined with durvalumab (pharmacokinetic sampling and analysis as defined in protocol)."}
• {"endpoint_text":"-Immunogenicity of dato-DXd in combination with durvalumab","definition_or_measurement_approach":"Assessment of immunogenicity (anti-drug antibodies) for Dato-DXd in combination with durvalumab."}
• {"endpoint_text":"-Safety & tolerability","definition_or_measurement_approach":"Safety and tolerability assessed by collection of adverse events, laboratory values, and other safety assessments per protocol."}

Italy

Earliest CTIS Part Ii Submission Date

02-09-2024

Latest Decision Or Authorization Date

29-01-2026

Processing Time Days

514

Number Of Sites

9

Number Of Participants

12

France

Earliest CTIS Part Ii Submission Date

29-11-2024

Latest Decision Or Authorization Date

04-02-2026

Processing Time Days

432

Number Of Sites

8

Number Of Participants

10

Spain

Earliest CTIS Part Ii Submission Date

07-11-2024

Latest Decision Or Authorization Date

02-02-2026

Processing Time Days

452

Number Of Sites

8

Number Of Participants

12

Poland

Earliest CTIS Part Ii Submission Date

30-09-2025

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

178

Number Of Sites

4

Number Of Participants

6

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden