Breast Cancer
Conditions
Interventions
Arm 1: Dato-DXd
Experimental: Dato-DXd
Experimental drug. Provided in 100mg vials. IV infusion.
Other Name: Datopotamab deruxtecan (Dato-DXd, DS-1062a)
Arm 2:
If no prior taxane, or prior taxane in t
Sponsors
Inoguchi Akihiro
AstraZeneca
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age 1. Participant must be >= 18 years at the time of screening. Type of Participant and Disease Characteristics 2. Histologically or cytologically documented locally recurrent inoperable TNBC, which cannot be treated with curative intent, or metastatic TNBC. TNBC is defined as: - Negative for ER with = 10 mm in the longest diameter (except lymph nodes, which must have short axis >= 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), and is suitable for accurate repeated measurements. 6. ECOG PS 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing. 7. Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, capecitabine, carboplatin, or eribulin), based on DFI and prior taxane exposure, per investigator assessment. 8. Has had an adequate treatment washout period before Cycle 1 Day 1, defined as: - Major surgery: >= 3 weeks. - Radiation therapy including palliative radiation to chest: >= 4 weeks (palliative radiation therapy to other areas >= 2 weeks). - Corticosteroid therapy for central nervous system metastatic disease: > 3 days. - Anti cancer therapy including hormonal therapy: >= 3 weeks (for small molecule targeted agents: >= 2 weeks or 5 half-lives, whichever is longer). - Nitrosoureas or mitomycin C: >= 6 weeks. - Antibody-based anti cancer therapy: >= 4 weeks with the exception of receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (eg, denosumab for the treatment of bone metastases). - Immunotherapy (non-antibody-based therapy), retinoid therapy: >= 2 weeks or 5 times the terminal elimination half-life of the agent, whichever is longer. - Chloroquine/hydroxychloroquine: > 14 days. 9. Written confirmation of tumour sample needs to be available prior to enrolment and tumour samples should be available prior to randomisation. All participants must have a FFPE metastatic (excluding bone) or locally recurrent inoperable tumour sample (block preferred, or a minimum of 20 freshly cut slides) available, collected <= 3 months prior to screening. If neither an adequate FFPE block nor the minimum of 20 slides are available from the most recent biopsy, or if a biopsy is not feasible for safety reasons, and this is clearly documented, an archival tumour specimen obtained before the diagnosis of locally recurrent inoperable or metastatic breast cancer may be submitted, pending approval by the Global Study Team. 10. Participants
Exclusion criteria
Exclusion criteria: Medical Conditions 1. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, uncontrolled hypertension, history of allogeneic organ transplant, and active bleeding diseases, ongoing or active infection, or significant cardiac or psychological conditions), 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. 2. 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 (per investigator assessment). 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. 3. Persistent toxicities caused by previous anti-cancer therapy, excluding alopecia, not yet improved to Grade 350 cells/mm3, no history of an acquired immune deficiency syndrome-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti-HIV medications. 7. Uncontrolled or significant cardiac disease including: - Myocardial infarction or uncontrolled/unstable angina within 6 months prior to Cycle 1 Day 1 - Congestive heart failure (New York Heart Association Class II to IV), or - Uncontrolled or significant cardiac arrhythmia, or - Uncontrolled hypertension (resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg). 8. Resting ECG with clinically abnormal findings. 9. Uncontrolled hypercalcaemia: > 1.5 mmol/L (> 6 mg/dL) ionised calcium, or serum calcium (uncorrected for albumin) > 3 mmol/L (> 12 mg/dL), or corrected serum calcium > ULN, or clinically significant (symptomatic) hypercalcaemia. 10. History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. 11. Has severe pulmonary function compromise. 12. Leptomeningeal carcinomatosis. 13. Clinically significant corneal disease. 14. Known active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice). Prior/Concomitant Therapy 15. Prior exposure to: - Any treatment (including ADC) containing a chemotherapeutic agent targeting topoisomerase I - TROP2-targeted therapy - Prior treatment with same ICC agent - Chloroquine/hydroxychloroquine without an adequate treatment washout period of > 14 days prior to randomisation. 16. Any concurren
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Progression Free Survival (PFS) [ Time Frame: From randomization until progression as assessed by BICR or death due to any cause (anticipated to be up to 26 months) ] PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression. 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 hazard ratio [HR] of PFS. 2. Overall Survival (OS) [ Time Frame: From randomisation until the date of death due to any cause (approximately 42 months) ] OS is defined as the time from randomisation until the date of death due to any cause. The analysis will include all randomised participants, by treatment group as randomised. The measure of interest is the hazard ratio [HR] of OS. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Objective Response Rate (ORR) [ Time Frame: From randomisation up until progression (anticipated to be up to 26 months) ] ORR is defined as the proportion of participants who have a confirmed CR or PR, as determined by BICR/investigator assessment, per RECIST 1.1. The analysis will include all randomised participants, by treatment group as randomised. Data obtained from randomisation up until progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of ORR, regardless of whether the participant withdraws from therapy. Participants who go off treatment without a response or progression, receive a subsequent anti-cancer therapy, and then respond will not be included as responders in the ORR. The measure of interest is the odds ratio of the ORR. 2. Duration of Response (DoR) [ Time Frame: From the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR/investigator assessment or death due to any cause (anticipated to be up to 26 months) ] 3. PFS by Investigator assessment [ Time Frame: From randomisation until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause (anticipated to be up to 26 months) ] PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression. The measure of interest is the hazard ratio [HR] of PFS. 4. Disease Control Rate (DCR) [Time Frame: At least 11 weeks after randomization to 23 months] DCR at 12 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 BICR/investigator assessment and derived from the raw tumour data for a | — |
Countries
Argentina, Belgium, Brazil, Canada, China, France, Germany, Hungary, India, Italy, Japan, Korea, Philippines, Poland, Republic of Mexico, Singapore, South Africa, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactContact for Clinical Trial Information
DAIICHI SANKYO Co.,Ltd.
Outcome results
None listed