2023-509260-25-00招募中3 期
A Phase 3, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) Versus Investigator’s Choice of Chemotherapy in Patients who are not Candidates for PD-1/PD-L1 Inhibitor Therapy in First-line Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPION-Breast02)
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 177
- 试验地点
- 55
- 主要终点
- PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
研究概览
简要总结
- 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.
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 主要目的
- Post-intervention follow-up period
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Participant must be ≥ 18 years at the time of screening.
- •Participants with a history of previously treated neoplastic spinal cord compression or asymptomatic, stable brain metastases, who require no treatment with corticosteroids or anticonvulsants may be included in the study, if they are no longer symptomatic and have recovered from acute toxic effects of radiotherapy. A minimum of 2 weeks must have elapsed between the end of radiotherapy and Cycle 1 Day
- •A minimum of 3 days must have elapsed between the end of corticosteroid therapy for central nervous system metastatic disease and Cycle 1 Day 1
- •Adequate organ and bone marrow function within 7 days before randomisation.
- •Minimum life expectancy of 12 weeks.
- •Male or female.
- •Negative pregnancy test (serum) for women of childbearing potential.
- •Female participants must be at least 1 year post-menopausal, surgically sterile, or using at least 1 highly effective form of birth control (a highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly.) 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 Cycle 1 Day 1 and continue for at least 7 months after the last dose. Female participants must refrain from egg cell donation or retrieval for their own use, and breastfeeding from enrolment throughout the study and for at least 7 months after the last dose of study drug. 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.
- •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 the time of screening throughout the total duration of the study and the drug washout period (at least 6 months after the last dose of study intervention), in addition to the female partner using a highly effective contraceptive method, to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same time period. Preservation of sperm should be considered prior to randomisation. Not engaging in heterosexual activity (sexual abstinence) for the duration of the study and drug washout period is an acceptable practice, if this is the preferred usual lifestyle of the participant. Periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
- •Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- •Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of sample for optional genetic research that supports Genomic Initiative.
- •Histologically or cytologically documented locally recurrent inoperable TNBC, which cannot be treated with curative intent, or metastatic TNBC.
- •No prior chemotherapy or other systemic anti-cancer therapy for metastatic or locally recurrent inoperable breast cancer.
- •Not a candidate for PD-1/PD-L1 inhibitor therapy.
- •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.
- •ECOG PS 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
- •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.
- •Has had an adequate treatment washout period before Cycle 1 Day
- •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.
排除标准
- •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.
- •Clinically significant corneal disease.
- •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 exposure to any treatment (including ADC) containing a chemotherapeutic agent targeting topoisomerase I, or to TROP2- targeted therapy.
- •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).
- •Known history of severe hypersensitivity reactions to other monoclonal antibodies.
- •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.
- •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 in the opinion of the investigator may be included (eg, hearing loss).
- •Known active or uncontrolled hepatitis B or C virus infection.
- •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, cluster of differentiation (CD)4+ count > 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.
- •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.
- •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
- •Has severe pulmonary function compromise.
- •Leptomeningeal carcinomatosis.
结局指标
主要结局
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
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 HR of OS
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 HR of OS
次要结局
- 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.
- 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.
- 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).
- Disease Control Rate (DCR): Defined as best overall response of CR or PR or SD (without subsequent cancer therapy) per RECIST 1.1, as assessed by BICR/per investigator assessment and maintained for ≥ 11 weeks from randomization. DCR at 12 weeks (DCR-12) is defined as the percentage of subjects who have disease control.
- 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.
- 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.
- 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 local standard clinical practice based on radiological or clinical progression.
- Clinical Outcome Assessments: TTD in a) pain (EORTC IL146), b) physical functioning (EORTC IL146), c) GHS/QoL (EORTC IL146), d) breast symptoms (EORTC IL116), e) arm symptoms (EORTC IL116).
- Pharmacokinetics
- Immunogenicity
- Safety & tolerability
研究者
AstraZeneca Clinical Study Information Center
Scientific
AstraZeneca AB
研究点 (55)
Loading locations...
相似试验
招募中
1 期
A Study of Dato-DXd Versus Investigator's Choice Chemotherapy in Patients with Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, who are not Candidates for PD-1/PD-L1 Inhibitor TherapyCTIS2023-509260-25-00AstraZeneca AB600
招募中
3 期
A Study of Dato-DXd Versus Investigator's Choice Chemotherapy in Patients With Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, Who Are Not Candidates for PD-1/PD-L1 Inhibitor TherapyBreast CancerJPRN-jRCT2061220029Inoguchi Akihiro600
招募中
1 期
A Study of Dato-DXd Versus Investigator's Choice Chemotherapy in Patients with Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, who are not Candidates for PD-1/PD-L1 Inhibitor Therapyocally Recurrent Inoperable or Metastatic Triple-negative Breast CancerMedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)EUCTR2021-005223-21-ITASTRAZENECA AB600
尚未招募
3 期
A Study of Dato-DXd Versus Investigators Choice Chemotherapy in Patientswith Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, who are not Candidates for PD-1/PD-L1 Inhibitor TherapyCTRI/2022/10/046630AstraZeneca Pharma India Ltd
进行中（未招募）
1 期
A Study of Dato-DXd Versus Investigator's Choice Chemotherapy in Patients with Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, who are not Candidates for PD-1/PD-L1 Inhibitor TherapyEUCTR2021-005223-21-DEAstraZeneca AB600