2023-505552-22-00招募中3 期
A Phase 3 Open-label, Randomised Study of Datopotamab Deruxtecan (DatoDXd) With or Without Durvalumab Versus Investigator's Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Who Have Residual Invasive Disease in the Breast and/or Axillary Lymph Nodes at Surgical Resection Following Neoadjuvant Systemic Therapy (TROPION-Breast03)
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 269
- 试验地点
- 89
- 主要终点
- Invasive disease-free survival (iDFS), defined as time from randomization until date of first event (local, regional, contralateral or distant breast cancer recurrence, second primary non-breast invasive cancer, or death from any cause. iDFS is based on investigator assessment. Analysis includes all randomised participants, regardless of withdrawal or receipt of another anticancer therapy. Measure of interest is HR of iDFS for Dato-DXd + durvalumab vs ICT.
研究概览
简要总结
To demonstrate superiority of Dato-DXd in combination with durvalumab relative to ICT by assessment of iDFS in participants with stage I to III TNBC with residual invasive disease at surgical resection following neoadjuvant therapy
研究设计
- 分配方式
- Na
- 主要目的
- Post-intervention follow-up
- 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
- 否
入选标准
- •1.Participant must be ≥ 18 years at the time of screening; Male or female 2.Histologically confirmed invasive TNBC 3.Residual invasive disease in the breast and/or axillary lymph node (s) at surgical resection following neoadjuvant therapy 4.Completed at least 6 cycles of neoadjuvant therapy containing an anthracycline and/or taxane with or without platinum chemotherapy, with or without pembrolizumab. 5.No evidence of locoregional or distance relapse 6.Surgical removal of all clinically evident disease in the breast and lymph nodes 7.FFPE tumor sample from residual invasive disease at surgery 8.No adjuvant systemic therapy. Radiotherapy (if indicated) delivered before start of study treatment 9.No more than 6 weeks between completion of post-operative radiation therapy and randomization. If no post-operative radiation therapy, no more than 16 weeks between the date of breast surgery and randomization 10.Eligible for one of the therapy options listed as ICT 11.No known germline BRCA1 or BRCA2 pathogenic mutation 12.Adequate organ and bone marrow function; LVEF ≥ 50% by echocardiogram or MUGA; ECOG 0 or 1
排除标准
- •1.Stage IV (metastatic) TNBC 2.History of prior invasive breast cancer or evidence of recurrent disease following preoperative therapy and surgery 3.Prior anticancer therapy with topoisomerase I ADC, TROP2-targeted therapy (e.g., Trodelvy), participated in clinical studies with T-DXd 4.Prior exposure to a PD-1/PD-L1 inhibitor other than pembrolizumab 5.Severe or uncontrolled medical conditions including systemic diseases, history of allogeneic organ transplant and active bleeding diseases, ongoing or active infection, serious chronic gastrointestinal conditions associated with diarrhea; infections; active or uncontrolled HBV or HCV uncontrolled HIV; active TB 6.Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved to Grade ≤1 7.History of ILD or severe pulmonary function compromise 8.Clinically significant corneal disease 9.Any known active or prior documented autoimmune or inflammatory disorders 10.Any known active liver disease 11.Uncontrolled or significant cardiac disease 12.Grade ≥2 peripheral neuropathy of any etiology 13.History of severe hypersensitivity to either drug substances or inactive ingredients of Dato-DXd or history of hypersensitivity to PD- 1/PD-L1 inhibitors or capecitabine
研究组 & 干预措施
Datopotamab deruxtecan
Test
干预措施: Datopotamab deruxtecan (Drug)
IMFINZI 50 mg/mL concentrate for solution for infusion.
Test
干预措施: IMFINZI 50 mg/mL concentrate for solution for infusion. (Drug)
MYCOPHENOLATE MOFETIL
Auxiliary
干预措施: MYCOPHENOLATE MOFETIL (Drug)
CAPECITABINE
Comparator
干预措施: CAPECITABINE (Drug)
PEMBROLIZUMAB
Comparator
干预措施: PEMBROLIZUMAB (Drug)
INFLIXIMAB
Auxiliary
干预措施: INFLIXIMAB (Drug)
结局指标
主要结局
Invasive disease-free survival (iDFS), defined as time from randomization until date of first event (local, regional, contralateral or distant breast cancer recurrence, second primary non-breast invasive cancer, or death from any cause. iDFS is based on investigator assessment. Analysis includes all randomised participants, regardless of withdrawal or receipt of another anticancer therapy. Measure of interest is HR of iDFS for Dato-DXd + durvalumab vs ICT.
Invasive disease-free survival (iDFS), defined as time from randomization until date of first event (local, regional, contralateral or distant breast cancer recurrence, second primary non-breast invasive cancer, or death from any cause. iDFS is based on investigator assessment. Analysis includes all randomised participants, regardless of withdrawal or receipt of another anticancer therapy. Measure of interest is HR of iDFS for Dato-DXd + durvalumab vs ICT.
次要结局
- 7. iDFS for Dato-DXd + durvalumab vs IC
- 1. DDFS is defined as time from randomisation to date of the first distant recurrence, occurrence of second primary non-breast invasive cancer (other than squamous or basal cell skin cancer), or death from any cause. DDFS will be determined based on investigator assessment. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy. Measure of interest will be HR of DDFS.
- 2. DDFS for Dato-DXd vs ICT
- 3. DDFS for Dato-DXd + durvalumab vs Dato-DXd
- 4. Overall Survival (OS): defined as time from randomization until date of death due to any cause. The analysis will include all randomised participants, as randomised regardless of whether the participant withdraws from randomised therapy or received another anticancer therapy. Measure of interest will be the HR of OS for Dato-DXd + durvalumab vs ICT
- 5. OS for Dato-DXd vs ICT
- 6. iDFS for Dato-DXd vs ICT
- 8. Clinical Outcome Assessments (PRO endpoints): Time to Deterioration (TTD) and actual scores: in physical function as measured by the PROMIS Physical Function Short Form 8c and GHS/QoL as measured by the GHS/QoL scale from the EORTC IL172. The measure of interest is the HR of TTD and physical function and GHS/QoL scores for Dato-DXd +/- durvalumab vs ICT
- 9. Fatigue as measured by PROMIS Fatigue Short Form 7a. The measure of interest is the proportion of participants experiencing different levels of fatigue and actual scores at 3, 6, 12 months for Dato-DXd +/- durvalumab vs ICT
- 10. Pharmacokinetics of Dato-DXd
- 11. Immunogenicity of Dato-DXd
- 12. Safety and tolerability
研究者
AstraZeneca Clinical Study Information Center
Scientific
Astrazeneca AB
研究点 (89)
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