A Phase 1, First in Human, Open-Label Multicenter Study to Evaluate ALX2004, an Antibody Drug Conjugate Targeting EGFR in Participants With Advanced or Metastatic Select Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 170
- 试验地点
- 8
- 主要终点
- Phase 1a: Incidence of dose limiting toxicities (DLTs)
研究概览
简要总结
A Phase 1, First in Human, Open-Label Multicenter Study to Evaluate ALX2004, an Antibody Drug Conjugate Targeting EGFR in Participants with Advanced or Metastatic Select Solid Tumors
详细描述
This study consists of Phase 1a Dose finding, comprising of Dose Escalation portion followed by Dose Exploration, and a Phase 1b Dose Expansion. The study will enroll previously treated advanced or metastatic non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), esophageal squamous cell carcinoma (ESCC) and colorectal cancer (CRC). Up to 170 patients are expected to be enrolled in the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Participants with locally advanced, recurrent or metastatic histologically confirmed HNSCC, NSCLC, ESCC, CRC; locally advanced or recurrent disease must not be amenable to resection with curative intent
- •Dose Escalation: Participants who have relapsed or progressed following prior anticancer therapy in the advanced/metastatic setting and for whom no approved or standard therapy is available.
- •Dose Exploration and Dose Expansion: The following tumor-specific criteria also apply. These cohorts will include all or a subset of these tumors.
- •HNSCC - Received no more than 3 prior lines of therapy in the advanced or metastatic setting
- •NSCLC - For participants with a targetable molecular alteration: received appropriate standard targeted therapy and no more than 2 prior lines of systemic chemotherapy in the advanced/metastatic setting. For participants without a targetable molecular alteration: received platinum-based chemotherapy and CPI (in combination or separately), and have received no more than 2 prior lines of systemic chemotherapy in the advanced/metastatic setting
- •ESCC - Received no more than 3 prior lines of therapy in the advanced/metastatic setting
- •CRC - For participants with a targetable molecular alteration (including dMMR or MSI-H): Received appropriate standard therapy for the alteration, at least 2 prior lines of systemic chemotherapy, and no more than 4 prior lines of therapy in the advanced/metastatic setting. For participants without a targetable molecule alteration: Received at least 2 prior lines of systemic chemotherapy (including an oxaliplatin-based chemotherapy), vascular endothelial growth factor (VEGF)-based therapy, and no more than 4 prior lines of therapy in the advanced/metastatic setting.
- •Adequate Bone Marrow Function
- •Adequate Renal & Liver Function
- •Adequate Performance Status
排除标准
- •Participants with disease suitable for local therapy with curative intent.
- •Has a life expectancy of less than 3 months and/or has rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) in the opinion of the treating investigator
- •Prior treatment with any ADCs that have an active TOP1 inhibitor-based component
研究组 & 干预措施
ALX2004 Phase 1a (Dose Escalation)
ALX2004 will be administered. Patients will be enrolled into escalating dose levels during the dose escalation phase
干预措施: ALX2004 (Drug)
ALX2004 Phase 1a (Dose Exploration)
ALX2004 will be administered. All or a subset of tumors tested in dose escalation will enroll into 1 or 2 dose levels during the dose exploration phase
干预措施: ALX2004 (Drug)
ALX2004 Phase 1b (Dose Expansion)
ALX2004 will be administered. Patients will receive the recommended phase 2 dose during the dose expansion phase
干预措施: ALX2004 (Drug)
结局指标
主要结局
Phase 1a: Incidence of dose limiting toxicities (DLTs)
时间窗: Up to 28 days
Phase 1a: Number and proportion of participants enrolled in the dose escalation phase who experience dose-limiting toxicities (DLTs), received at least one dose of ALX2004 and completed the DLT evaluation
Phase 1a: Incidence of treatment emergent adverse events
时间窗: Up to 2 years from first dose
Phase 1a: Adverse Events as characterized by type, frequency, severity (NCI CTCAE v5.0), timing, seriousness, and relationship to the study drug in order to establish the RDE. Laboratory abnormalities as characterized by type, frequency, severity and timing
Phase 1b: Overall Response Rate (ORR) per investigator assessment using RECIST v1.1
时间窗: Up to 2 years from first patient dosed in dose expansion phase
Phase 1b: ORR is defined as proportion of participants whose BOR is complete response (CR) or partial response (PR)
次要结局
- Phase 1a and 1b: Clearance (CL)(Up to 2 years)
- Phase 1a and 1b: Area under the concentration time curve (AUC)(Up to 2 years)
- Phase 1a and 1b: Maximum Concentration (Cmax)(Up to 2 years)
- Phase 1a and 1b: Time of Maximum Plasma Concentration (Tmax)(Up to 2 years)
- Phase 1a and 1b: Terminal elimination half-life (t1/2)(Up to 2 years)
- Phase 1a and 1b: Progression Free Survival (PFS)(Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase)
- Phase 1a and 1b: Overall Survival (OS)(Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase)
- Phase 1a and 1b: Best Overall Response (BOR)(Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase)
- Phase 1a: Overall Response Rate (ORR) per investigator assessment using RECIST v1.1(Up to 2 years from first dose)
- Phase 1a and 1b: DCR (Disease Control Rate)(Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase)
- Phase 1a and 1b: Duration of Response (DoR)(Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase)
- Phase 1a and 1b: Evaluate the immunogenicity of ALX2004(Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase)
- Phase 1b: Incidence of treatment emergent adverse events(Up to 2 years from first patient dosed in dose expansion phase)