Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Carbo-Cell 10 mg/ml concentrate for solution for infusion
Product Name: Carboplatin
Product Code: [Carboplatin]
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed I
Sponsors
ASTRAZENECA AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be = 18 years (= 20 years in Japan) at the time of screening. 2. Histologically or cytologically documented locally recurrent inoperable or metastatic TNBC. 3. No prior chemotherapy or targeted systemic therapy for metastatic or locally recurrent inoperable breast cancer. 4. Not a candidate for PD 1/PD L1 inhibitor therapy. 5. At least 1 measurable lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as = 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), per investigator assessment. 8. Has had an adequate treatment washout period before Cycle 1 Day 1. 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 with a history of previously treated neoplastic spinal cord compression or clinically inactive brain metastases, who require no treatment with corticosteroids or anticonvulsants may be included in the study, if they have recovered from acute toxic effects of radiotherapy. A minimum of 2 weeks must have elapsed between the end of radiotherapy and study enrolment. A minimum of 3 days must have elapsed between the end of corticosteroid therapy for central nervous system metastatic disease and study enrolment. 11. Adequate organ and bone marrow function within 7 days before day of first dosing. 12. Minimum life expectancy of 12 weeks. 13. Male or female. 14. Negative pregnancy test (serum) for women of childbearing potential. 15.Female participants must be at least 1 year post-menopausal, surgically sterile, or using at least 1 highly effective form of birth control (failure rate of less than 1% per year). Women of childbearing potential who are sexually active with a non sterilised male partner must agree to use at least 1 highly effective method of birth control. They should have been stable on their chosen method of birth control for a minimum of 3 months before entering the study and continue for at least 7 months after the last dose. Must refrain from egg cell donation and breastfeeding for this period. Any non sterilised male partner of a woman of childbearing potential must use a male condom plus spermicide (condom alone in countries where spermicides are not approved) throughout this period. 16.Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or use an acceptable method of contraception from screening
Exclusion criteria
Exclusion criteria: 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) 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 basal cell carcinoma of the skin and squamous cell carcinoma of the skin that have undergone potentially curative therapy, adequately resected nonmelanoma skin cancer, curatively treated in situ disease, or other solid tumours curatively treated. 3. Persistent toxicities caused by previous anti cancer therapy, excluding alopecia, not yet improved to Grade = 1 or baseline. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss) after consultation with the sponsor study clinical lead or designee. 4. Uncontrolled infection requiring IV antibiotics, antivirals or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections (participants with localised fungal infections of skin or nails are eligible). 5. Known active or uncontrolled hepatitis B or C virus infection; or is positive for hepatitis B or C virus, based on the evaluation of tests for hepatitis B or hepatitis C infection at screening. 6. Known human immunodeficiency virus (HIV) infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load, cluster of differentiation (CD)4+ count > 250 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 8. 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. 9. 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 10. Clinically severe pulmonary function compromise. 11. Leptomeningeal carcinomatosis. 12. Clinically significant corneal disease. 13. Known active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice). 14. Prior exposure to any treatment (including ADC) containing a chemotherapeutic agent targeting topoisomerase I, or to TROP2-targeted therapy 15. Concomitant use of chronic systemic (IV or oral) corticosteroids or other immunosuppressive medications except for managing AEs (inhaled steroids or intra articular steroid injections are permitted in this study). 16. Known severe hypersensitivity to Dato DXd or any of the excipients of the product, including but not limited to polysorbate 80.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To demonstrate superiority of Dato-DXd relative to ICC by assessment of PFS in participants with locally recurrent inoperable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy, per BICR. 2. To demonstrate superiority of Dato-DXd relative to ICC by assessment of OS in participants with locally recurrent inoperable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy.;Secondary Objective: 1) To demonstrate superiority of Dato-DXd relative to ICC by assessment of 1) ORR, 2) DoR, 3) PFS by investigator assessment, 4) DCR. To assess in participants treated with Dato-DXd compared to ICC TTD in 5) Pain, 6) Physical functioning, 7) Breast and arm symptoms, and 8) GHS/QoL. To demonstrate superiority of Dato-DXd relative to ICC by assessment of 9) TFST, 10) TSST, 11) PFS2. 12) To assess the pharmacokinetics of Dato-DXd. 13) To investigate the immunogenicity of Dato-DXd. 14) To assess the safety and tolerability of Dato-DXd compared with ICC in the safety analysis set.;Primary end point(s): 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 HR of PFS. 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. La misura di interesse è l'Hazard Ratio (HR) della OS.;Timepoint(s) of evaluation of this end point: For PFS, from randomization until progressi | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Objective Response Rate: Objective response rate is defined as the proportion of participants who have a confirmed CR or PR, as determined by the BICR/Investigator assessment, per RECIST 1.1. 2. Duration of Response: Duration of response is defined as the time 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. 3. Progression-Free Survival 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 (by any cause in the absence of progression), (ie, date of event or censoring – date of randomization + 1). 4. Disease Control Rate: Disease control rate 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 BICR/per investigator assessment and derived from the raw tumor data for at least 11 weeks after randomization. 5. 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. 6. 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. 7. 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 of the 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 loc | — |
Countries
Argentina, Belgium, Brazil, Canada, China, France, Germany, Hungary, India, Italy, Japan, Korea, Republic of, Mexico, Poland, Russian Federation, Singapore, South Africa, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed