Antibody-based PET Imaging and Treatment Response in Breast Cancer Treated With an Antibody-drug Conjugate According to Current Standard Indications.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- UNICANCER
- 入组人数
- 30
- 主要终点
- Metabolic objective response rate
研究概览
简要总结
OASIS-ImmunoPET is a monocentric pilot study evaluating antibody imaging to predict response to antibody-drug conjugate (ADC), an innovative cancer targeted therapy, and potentially replace tumor biopsy. It is addressed to patients with locally advanced or metastatic breast cancer who are eligible to receive the ADC Trastuzumab deruxtecan (T-DXd) according to local approval, and who are already enrolled in OASIS study (NCT pending).
详细描述
Antibody-drug conjugates (ADCs) have emerged as a transformative class of cancer targeted therapies, combining the specificity of monoclonal antibodies with the potency of cytotoxic payloads. This dual mechanism allows ADCs to selectively target tumor cells while minimizing systemic toxicity, thereby offering a more refined approach compared to conventional chemotherapy.
ADCs are made of 3 components: a monoclonal antibody specifically targeting tumor cells, a highly potent cytotoxic payload, and a special linker that connects the antibody to the drug. Their multi-step mode of action implies that ADC activity relies on multiple factors, such as target distribution, target density, internalization capability, linker cleavage, payload sensitivity and tumor-microenvironment modulation.
Over the past decade, ADCs have demonstrated significant improvements in survival for patients with various solid tumors and hematological malignancies. Despite these advancements, resistance to ADCs remains a major clinical challenge. Most patients who initially respond to ADC therapy eventually develop resistance, leading to disease progression. The mechanisms underlying ADC resistance are complex and poorly understood, involving tumor heterogeneity, drug metabolism, immune evasion, and alterations in target antigen expression.
Currently, no validated predictive biomarkers exist to guide ADC selection, treatment sequencing, or resistance monitoring. As a result, clinicians lack reliable tools to personalize ADC therapy, limiting the ability to optimize patient outcomes. A deeper understanding of ADC response and resistance mechanisms is urgently needed to define and adopt optimal companion diagnostics for currently approved and forthcoming ADCs and to obtain decision support tools for selecting the optimal ADC for each patient.
The protocol OASIS (NCT pending) aims to define optimal assays for predicting resistance to several approved ADCs in patients treated according to standard indications. The OASIS-ImmunoPET protocol will explore the potential contribution of advanced molecular imaging to identify response to treatment in patients enrolled in the OASIS study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent;
- •Patients enrolled in the prospective cohort of the OASIS study;
- •Patient with locally advanced or metastatic breast cancer eligible to receive T-DXd as part of their standard care;
- •At baseline imaging at least two "target" lesions fulfilling the following criteria: (1) anatomically transaxial diameter ≥ 1.5 cm and measurable per RECIST1.
- •and (2) metabolically assessable with a maximum standard uptake value corrected for lean body mass (SUVmax) ≥ 1.5 x SUVmean + 2 standard deviations (SD) of the liver measured in a 3-cm-diameter spherical volume of interest (VOI) in normal liver parenchyma;
- •Patients must be willing and able to comply with the protocol for the duration of the trial;
排除标准
- •Patients already treated with Trastuzumab deruxtecan (T-DXd);
- •Hypersensitivity at the ImmunoPET radioligands injection;
- •Patients who are claustrophobic or unable to remain still for 30 minutes;
- •Female participant who is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 90 days after the final administration of study treatment;
- •Person deprived of their liberty or under protective custody or guardianship.
研究组 & 干预措施
Locally advanced or metastatic breast cancer treated with Trastuzumab deruxtecan (T-DXd)
Experimental advanced molecular imaging (ImmunoPET) combining the high sensitivity and resolution of positron emission tomography (PET) with the specificity of ADC target specific monoclonal antibodies.
干预措施: Immuno-PET (Procedure)
结局指标
主要结局
Metabolic objective response rate
时间窗: From treatment initiation to disease progression, up to 3 cycles of treatment (each cycle is 21 to 28 days).
Metabolic objective response rate (ORR) is defined as the proportion of patients who achieved a confirmed complete metabolic response (CR) or partial metabolic response (PR) assessed by investigators according to PERCIST 1.0 after 3 cycles of treatment initiation.
次要结局
- Metabolic objective response rate (ORR) at 6 months(From treatment initiation to disease progression, up to 6 months of treatment)
- Radiological objective response rate (ORR)(From treatment initiation to objective response, up to 6 months)
- Radiological progression-free survival (PFS)(From treatment initiation to disease progression or death, up to 3 years)
- Proportion of patients with change in the pattern from baseline to progression or end of treatment(From treatment initiation to disease progression or death, up to 3 years)
- Progression-Free Survival (PFS)(From treatment initiation to disease progression or death, up to 3 years)
- Overall Survival (OS)(From treatment initiation to death from any cause, up to 5 years)
- Time to detection of brain metastases(From treatment initiation to brain metastasis onset, up to 5 years)