CTRI/2024/04/065629招募中3 期
A Phase III, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) With or Without Durvalumab Compared with Investigator’s Choice of Chemotherapy (Paclitaxel, Nab paclitaxel or Gemcitabine + Carboplatin) in Combination With Pembrolizumab in Patients with PD L1 Positive Locally Recurrent Inoperable or Metastatic Triple negative Breast Cancer (TROPION Breast- 05)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 657
- 试验地点
- 15
- 主要终点
- Progression Free Survival (PFS) assessed by BICR (Blinded Independent Central Review) for Arm 1 Vs Arm 2
研究概览
简要总结
A Phase III, Open label, Randomised Study of Datopotamab Deruxtecan Dato DXd in Combination With or without Durvalumab Compared with Investigator’s Choice of Chemotherapy Paclitaxel, Nab paclitaxel or Gemcitabine Plus Carboplatin in Combination With Pembrolizumab in Patients with PD L1 Positive Locally Recurrent Inoperable or Metastatic Triple negative Breast Cancer TROPION Breast05.The target population of interest in this study is participants 18 years with PD L1 positive locally recurrent inoperable or metastatic TNBC .Participants must not have received TOPO I based ADC and be eligible for ICC paclitaxel, nab paclitaxel, or gemcitabine Plus carboplatin and pembrolizumab. All participants will receive study intervention until investigator assessed progression of disease PD according to RECIST 1.1 or until unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met. Crossover within the study will not be permitted. Switching between ICC agents is not permitted.
Follow up of participants post discontinuation of study intervention:
After study treatment discontinuation, all participants will undergo an end of treatment visit and safety follow up visits at protocol defined period
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Inclusion Criteria Age 1 Participant must be 18 years at the time of signing the informed consent form ICF.
- •Type of Participant and Disease Characteristics 2 Histologically or cytologically documented locally recurrent inoperable, which cannot be treated with curative intent, or metastatic TNBC.
- •TNBC is defined as: Negative for ER with of tumour cells positive for ER on IHC.
- •Negative for progesterone receptor with 1 of tumour cells positive for progesterone receptor on IHC.
- •Negative for HER2 with 0 or 1 intensity on IHC or 2 intensity on IHC and negative by in situ hybridisation per the ASCO-CAP HER2 guidelines 3 ECOG PS 0 or 1 with no deterioration over the previous 2 weeks prior to randomisation.
- •4 All participants must provide a FFPE metastatic excluding bone or locally recurrent inoperable tumour sample collected 3 months prior to signing of informed consent ie, start of screening..
- •5 PD L1 positive TNBC based on results from an appropriately validated investigational PD L1 22C3 assay CPS 10 from a sponsor-designated central laboratory.
- •6 No prior chemotherapy or targeted systemic anti-cancer therapy for metastatic or locally recurrent inoperable breast cancer.
- •7 Eligible for one of the chemotherapy options listed as ICC paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin 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 CNS metastatic disease: 3 days.
- •Anticancer therapy including hormonal therapy: 3 weeks for small molecule targeted agents: 2 weeks or 5 half-lives, whichever is longer.
- •Chloroquine/hydroxychloroquine: 14 days.
- •9 Measurable disease by computed tomography CT or MRI as per RECIST 1.
- •10 Adequate bone marrow reserve and organ function within 7 days before Cycle 1 Day 1 as follows 11 Minimum life expectancy of 12 weeks.
- •Sex and Contraceptive/Barrier Requirements 12 Male or female.
- •Reproduction Contraceptive use by females or males should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
排除标准
- •Exclusion Criteria Medical Conditions 1 As judged by the investigator, any evidence of diseases 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 with exceptions as defined in protocol 3 Persistent toxicities caused by previous anticancer therapy 4 Neoplastic spinal cord compression or active brain metastases 5 Has significant third-space fluid retention and is not amenable for required repeated drainage. 6 Uncontrolled infection requiring IV antibiotics, antivirals or antifungals; suspected infections ; or inability to rule out infections 7 Has active or uncontrolled hepatitis B or C virus infection. 8 Known HIV infection that is not well controlled. 9 Uncontrolled or significant cardiac disease 10 Participant meets one or more of the following, as judged by the investigator: Mean resting corrected QT interval corrected by Fridericia’s formula QTcF 470 ms regardless of gender, obtained from a single 12-lead electrocardiogram ECG performed at screening. History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and/or cause Torsades de Pointes. Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives. 11 Uncontrolled hypercalcaemia 12 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. 13 Has severe pulmonary function compromise. 14 Leptomeningeal carcinomatosis or history of leptomeningeal carcinomatosis. 15 Clinically significant corneal disease. 16 Active or prior documented autoimmune or inflammatory disorders Prior Concomitant Therapy 17 Prior exposure to: a.
- •Any treatment including ADC containing a chemotherapeutic agent targeting topoisomerase I. b.
- •TROP2-targeted therapy. c.
- •Chloroquine/hydroxychloroquine without an adequate treatment washout period of 14 days prior to randomisation. 18 Any concurrent anticancer treatment. 19 Concurrent use of systemic hormone replacement therapy (HRT eg, oestrogen and or progesterone or hormonal contraception. However, concurrent use of hormones for other non cancer related conditions eg, insulin for diabetes is acceptable. 20 Current or prior use of immunosuppressive medication within 14 days prior to randomisation. 21 Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention 22 Major surgical procedure or significant traumatic injury 3 weeks of Cycle 1 Day 1 or an anticipated need for major surgery during the study.
结局指标
主要结局
Progression Free Survival (PFS) assessed by BICR (Blinded Independent Central Review) for Arm 1 Vs Arm 2
时间窗: The primary (and final) PFS analysis for superiority will be performed after approximately 336 BICR PFS events have occurred across the Dato-DXd + durvalumab and ICC + pembrolizumab treatment groups (61% maturity).
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
时间窗: The primary (and final) PFS analysis for superiority will be performed after approximately 336 BICR PFS events have occurred across the Dato-DXd + durvalumab and ICC + pembrolizumab treatment groups (61% maturity).
The comparison will include all randomised participants, as randomized.
时间窗: The primary (and final) PFS analysis for superiority will be performed after approximately 336 BICR PFS events have occurred across the Dato-DXd + durvalumab and ICC + pembrolizumab treatment groups (61% maturity).
次要结局
- To demonstrate superiority of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of OS in participants with PD L1 positive locally recurrent inoperable or metastatic TNBC(OS is defined as the time from randomisation until the date of death due to any cause.)
- To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of ORR in participants with PD L1 positive locally recurrent inoperable or metastatic TNBC.(ORR is defined as the proportion of participants who have a CR or PR, as determined by the BICR/investigator assessment, per RECIST 1.1.)
- To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of DoR in participants with PD L1 positive locally recurrent inoperable or metastatic TNBC.(DoR 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)
- To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of PFS as assessed by the investigator in participants with PD L1 positive locally recurrent inoperable or metastatic TNBC.(PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator, or death due to any cause.)
- To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of CBR at 24 weeks in participants with PD L1 positive locally recurrent inoperable or metastatic TNBC.(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.)
- To assess TTD in breast and arm symptoms in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab.(TTD in breast symptoms as measured by the breast symptoms scale from EORTC IL116)
- To assess TTD in pain in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab.(TTD in pain as measured by the EORTC IL199.)
- To assess TTD in physical functioning in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab.(TTD in physical function as measured by the PROMIS Short Form v2.0 – Physical Function 8c.)
- To assess TTD in GHS/QoL in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab.(TTD in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172.)
- To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of TFST in participants with PD L1 positive locally recurrent inoperable or metastatic TNBC.(TFST is defined as the time from randomisation until the start date of the first subsequent anticancer therapy after discontinuation of randomised treatment, or death due to any cause)
- To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of TSST in participants with PD L1 positive locally recurrent inoperable or metastatic TNBC.(TSST is defined as the time from randomisation until the start date of the second subsequent anticancer therapy after discontinuation of first subsequent treatment, or death due to any cause.)
- To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of PFS2 in participants with PD L1 positive locally recurrent inoperable or metastatic TNBC.(PFS2 will be defined as the time from the randomisation to the earliest progression event (following the initial investigator-assessed progression), subsequent to first subsequent therapy, or death.)
- To assess the pharmacokinetics of Dato DXd (6 mg/kg IV Q3W) in combination with durvalumab.(Concentration of Dato-DXd, total anti-TROP2 antibody, and DXd (payload) in plasma.)
- To investigate the immunogenicity of Dato-DXd (6 mg/kg IV Q3W) in combination with durvalumab.(Presence of antidrug antibodies for Dato-DXd (confirmatory results: positive or negative, titres).)
- To assess the safety & tolerability of Dato-DXd + durvalumab as compared with ICC + pembrolizumab in the safety analysis set of participants with PD L1 positive locally recurrent inoperable or metastatic TNBC.(Safety & tolerability will be evaluated in the safety population in terms of AEs (graded by CTCAE version 5.0) & in terms of:)
研究者
Mr Sandeep AV
AstraZeneca Pharma India Ltd
研究点 (15)
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