A Multicenter, Open-label, Phase 1 Clinical Trial to Evaluate the Safety and Anti-Tumor Activity of AB-201 in Subjects With Advanced Human Epidermal Growth Factor Receptor 2 Positive(HER2+) Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 48
- 主要终点
- Determination of Recommended Phase 2 Dose (RP2D)
研究概览
简要总结
This clinical trial will enroll subjects with HER2+ solid tumors and is conducted in two phases, which are phase 1a and phase 1b. The primary objective of phase 1 is to determine the safety and tolerability of AB-201 in subjects with advanced HER2+ solid tumors.
详细描述
This is a Phase 1, multicenter study designed to evaluate the safety, tolerability, and efficacy of AB-201 in subjects with advanced HER2+ solid tumors (specifically, breast and gastric/GEJ cancers).
The Phase 1 will be conducted in two parts, an initial dose escalation stage followed by a dose expansion stage.
Study participation for each subject begins with up to 28 days (1 month) of screening following written informed consent, then lymphodepletion treatment, followed by AB-201. Up to 3 doses of AB-201 may be administered. All subjects will be monitored for a total duration of 18 months of follow up from the first dose administration of AB-201.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 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
- •ECOG performance status 0 to
- •Histologically confirmed HER2 expressed breast or gastric/GEJ cancer IHC ≥ 2+ within 6 months prior to study entry.
- •Confirmed diagnosis of an advanced/unresectable or metastatic HER2+ breast or gastric/GEJ cancer that is refractory to, or intolerable of standard treatment, or for which no standard treatment is available.
- •Must have received prior cancer therapy: Subjects with breast cancer must have received ≥ 3 prior systemic therapies; subjects with gastric/GEJ cancer must have received ≥ 2 prior systemic therapy(ies); subjects with IHC 3+ or IHC 2+/ISH+ cancers must have received previous treatment with a HER2-targeting therapy.
排除标准
- •Known past or current malignancy other than inclusion diagnosis.
- •Known clinically significant cardiac disease.
- •Active central nervous system (CNS) metastases, or involvement of the CNS, unless there is a history of at least 3 months of sustained remission.
- •Unresolved toxicities from prior anticancer therapy.
- •Ongoing uncontrolled systemic infections requiring antibiotic, anti-fungal, or anti-viral therapy.
- •History of sensitivity or intolerance to cyclophosphamide or fludarabine.
- •Currently Pregnant or lactating
- •Severe disease progression or health deterioration within 2 weeks prior to lymphodepletion regimen.
研究组 & 干预措施
Phase 1a Dose Escalation
-
Dose Escalation of AB-201 in advanced metastatic breast cancer, gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression
-
Interventions:
-
Drug: AB-201
-
Drug: Cyclophosphamide
-
Drug: Fludarabine
干预措施: AB-201 (Drug)
Phase 1a Dose Escalation
-
Dose Escalation of AB-201 in advanced metastatic breast cancer, gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression
-
Interventions:
-
Drug: AB-201
-
Drug: Cyclophosphamide
-
Drug: Fludarabine
干预措施: Cyclophosphamide (Drug)
Phase 1a Dose Escalation
-
Dose Escalation of AB-201 in advanced metastatic breast cancer, gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression
-
Interventions:
-
Drug: AB-201
-
Drug: Cyclophosphamide
-
Drug: Fludarabine
干预措施: Fludarabine (Drug)
Phase 1b Dose Expansion
-
Dose Confirmation of AB-201 in advanced metastatic breast cancer, gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression
-
Interventions:
-
Drug: AB-201
-
Drug: Cyclophosphamide
-
Drug: Fludarabine
干预措施: AB-201 (Drug)
Phase 1b Dose Expansion
-
Dose Confirmation of AB-201 in advanced metastatic breast cancer, gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression
-
Interventions:
-
Drug: AB-201
-
Drug: Cyclophosphamide
-
Drug: Fludarabine
干预措施: Cyclophosphamide (Drug)
Phase 1b Dose Expansion
-
Dose Confirmation of AB-201 in advanced metastatic breast cancer, gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression
-
Interventions:
-
Drug: AB-201
-
Drug: Cyclophosphamide
-
Drug: Fludarabine
干预措施: Fludarabine (Drug)
结局指标
主要结局
Determination of Recommended Phase 2 Dose (RP2D)
时间窗: up to 18 months per patient
Assessment of Dose-Limiting Toxicities(DLTs), pharmacokinetics (PK), safety, and objective response rate (ORR) per the Response Evaluation Criteria for Solid Tumors (RECIST) v1.1 in subjects with HER2+ breast cancer and gastric/GEJ cancer. PK: Monitor persistence of AB-201 in subjects samples collected prior to and following AB-201 administration.
Incidence, severity, seriousness, and dose relationship of Adverse Events [Safety & Tolerability]
时间窗: up to 18 months per patient
Adverse events and laboratory abnormalities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
次要结局
- To determine the preliminary efficacy, by the objective response rate (ORR) per the Response Evaluation Criteria for Solid Tumors (RECIST) v1.1, of AB-201 in subjects with advanced HER2+ solid tumors(up to 18 months per patient)