A Phase IB/II, 2-stage, Open-label, Multicenter Study to Determine the Efficacy and Safety of Durvalumab (MEDI4736) + Paclitaxel and Durvalumab (MEDI4736) in Combination With Novel Oncology Therapies With or Without Paclitaxel for First-line Metastatic Triple Negative Breast Cancer
概览
- 阶段
- 1 期
- 干预措施
- Durvalumab
- 疾病 / 适应症
- Triple Negative Breast Neoplasms
- 发起方
- AstraZeneca
- 入组人数
- 243
- 试验地点
- 33
- 主要终点
- Dose Limiting Toxicity (DLT) Events
- 状态
- 进行中（未招募）
- 最后更新
- 8天前
概览
简要总结
This study is designed to determine the efficacy and safety of durvalumab in combination with novel oncology therapies with or without paclitaxel and durvalumab + paclitaxel for first-line metastatic triple negative breast cancer
详细描述
This is a Phase IB/II, 2-stage, open-label, multicenter study to determine the efficacy and safety of durvalumab in combination with novel oncology therapies (i.e. therapies designed for immune modulation) with or without paclitaxel and durvalumab + paclitaxel as first-line treatment in patients with metastatic triple negative breast cancer (TNBC). The study is designed to concurrently evaluate potential novel treatment combinations with clinical promise using a 2-stage approach. The study will use a Simon 2-Stage design to evaluate which cohorts may proceed to expansion. Part 1 is a Phase IB study of safety and initial efficacy, and Part 2 may expand patient enrollment if adequate efficacy signal is observed in Part 1. The treatment regimens evaluated in Part 2 will depend on the evaluation of safety and efficacy outcomes in Part 1.
研究者
入排标准
入选标准
- •At least 18 years of age at the time of screening
- •Patient must have locally confirmed advanced/unresectable or metastatic TNBC.
- •No prior treatment for metastatic (Stage IV) TNBC
- •Patient must have at least 1 lesion, not previously irradiated, that can be accurately measured
- •WHO/ECOG status at 0 or 1 at enrollment
- •Patients enrolled to Arm 6 (durvalumab and DS-8201a) Must provide documentation of locally determined advanced/unresectable or metastatic TNBC with HER2 low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested)
- •Patients enrolled in Arm 8 (durvalumab + Dato-DXd) Must have PD-L1 positive tumor as determined by an IHC based assay
排除标准
- •History of allogeneic organ transplantation
- •Active or prior documented autoimmune or inflammatory disorders
- •Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen \[HBsAg\] result), hepatitis C virus (HCV), or human immunodeficiency virus (positive HIV 1/2 antibodies)
- •Untreated CNS metastases
- •Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
- •Any concurrent chemotherapy, IP, or biologic therapy for cancer treatment
- •Female patients who are pregnant, breastfeeding
- •Cardiac Ejection Fraction less than 50%
- •Patients enrolled in Arm 2 only:
- •Potent inhibitors or inducers or substrates of CYP3A4 or substrates of CYP2C9 or CYP2D6 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort)
研究组 & 干预措施
Arm 1
durvalumab + paclitaxel
干预措施: Durvalumab
Arm 1
durvalumab + paclitaxel
干预措施: Paclitaxel
Arm 2
durvalumab + paclitaxel + capivasertib
干预措施: Durvalumab
Arm 2
durvalumab + paclitaxel + capivasertib
干预措施: Capivasertib
Arm 5
durvalumab + paclitaxel + oleclumab
干预措施: Oleclumab
Arm 5
durvalumab + paclitaxel + oleclumab
干预措施: Paclitaxel
Arm 6
durvalumab + trastuzumab deruxtecan
干预措施: Durvalumab
Arm 2
durvalumab + paclitaxel + capivasertib
干预措施: Paclitaxel
Arm 5
durvalumab + paclitaxel + oleclumab
干预措施: Durvalumab
Arm 6
durvalumab + trastuzumab deruxtecan
干预措施: Trastuzumab deruxtecan
Arm 7
durvalumab + datopotamab deruxtecan
干预措施: Durvalumab
Arm 7
durvalumab + datopotamab deruxtecan
干预措施: Datopotamab deruxtecan
Arm 8
durvalumab + datopotomab deruxtecan (patients with PD-L1 positive status)
干预措施: Durvalumab
Arm 8
durvalumab + datopotomab deruxtecan (patients with PD-L1 positive status)
干预措施: Datopotamab deruxtecan
结局指标
主要结局
Dose Limiting Toxicity (DLT) Events
时间窗: From the time of first dose until completion of the first cycle (28 days for Arms 2-5, 21 days for Arms 6-7 (no safety run-in for Arms 1 and 8))
The occurrence of a severe adverse event (meeting pre-specified criteria) that is at least possibly related to durvalumab and/or the novel oncology therapy in 6 DLT-evaluable patients
次要结局
- Objective Response Rate (ORR)(Tumor assessments: every 8 wks (Arms 1-5) or every 6 wks (Arms 6-8) until wk 48, then every 12 wks from first IP dose until radiologic progression, death, withdrawal of consent, or study completion; up to max 54 mos (observed longest duration in Arm 1))
- Progression-free Survival (PFS)(Tumor assessments: every 8 wks (Arms 1-5) or every 6 wks (Arms 6-8) until wk 48, then every 12 wks from first IP dose until radiologic progression, death, withdrawal of consent, or study completion; up to max 54 mos (observed longest duration in Arm 1))
- Duration of Response (DoR)(Tumor assessments: every 8 wks (Arms 1-5) or every 6 wks (Arms 6-8) until wk 48, then every 12 wks from first IP dose until radiologic progression, death, withdrawal of consent, or study completion; up to max 54 mos (observed longest duration in Arm 1))
- Overall Survival (Count)(From date of first dose until date of death due to any cause; up to the maximum of 54 months (observed longest duration in Arm 1))
- Overall Survival (Duration)(From date of first dose of IP until date of death due to any cause; up to the maximum of 54 months (observed longest duration in Arm 1))
- Progression-free Survival at 6 Months (PFS6)(6 months following date of first dose)