A Phase 1 Dose Escalation and Cohort Expansion Study of ERY974, An Anti-Glypican3 (GPC3)/CD3 Bispecific Antibody, in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 主要终点
- Dose escalation： MTD determination
研究概览
简要总结
This is the open label, multicenter Phase 1 study which consists of a dose escalation to determine the maximum tolerated dose (MTD) and cohort expansion to obtain a preliminary evaluation of anti-tumor activity. ERY974 is intravenously injected to patients with Glypican 3 positive advanced solid tumors until unacceptable toxicity or disease progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Male or female patient with Glypican 3 positive advanced solid tumor not amenable to standard therapy or for which standard therapy is not available or not indicated
- •Measurable tumor
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- •Adequate bone marrow, liver, and renal function
- •Adequate coagulation status
排除标准
- •Patients with more than a single brain metastasis ( >1 cm)
- •Patients with acute or chronic infection
- •Major surgery within 28 days
- •Pregnant or lactating women
- •Patients with interstitial pneumonitis
- •Patients require regular ascites/pleural effusion drainage
研究组 & 干预措施
Dose escalation cohort of ERY974
Dose escalation (DE) will proceed with the dose level increment and the dose cohort size being guided by a safety evaluations during and at the end of each cohort. DE initially utilizes an accelerated titration design (ATD) and once the first dose limiting toxicity (DLT) is observed, DE will continue using a modified continual reassessment method (mCRM) until MTD.
干预措施: ERY974 (Drug)
Cohort expansion in gastric cancer
Patients with GPC3 positive advanced gastric cancer or gastroesophageal junction cancer will receive ERY974 at recommended dose until disease progression.
干预措施: ERY974 (Drug)
Cohort expansion in esophageal carcinoma
Patients with GPC3 positive advanced squamous cell esophageal carcinoma will receive ERY974 at recommended dose until disease progression.
干预措施: ERY974 (Drug)
Cohort expansion in other solid tumors
Patients with other GPC3 positive advanced solid tumors will receive ERY974 at recommended dose until disease progression
干预措施: ERY974 (Drug)
结局指标
主要结局
Dose escalation： MTD determination
时间窗: DLT evaluation period, defined as from the first ERY974 injection until 7 days after the third injection
Determination of dose-limiting toxicities (DLT)
Cohort expansion：Preliminary assessment of change in tumor size
时间窗: From the date of informed consents obtained until disease progression: at screening , week 6,12,18 and subsequently every 3 months up to 38 months
Anti-tumor activity will be assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST)
次要结局
- Dose escalation： Number and severity of adverse events(Adverse events will be reported through 28 days after the last dose)
- Dose escalation：terminal half-life(PK will be assessed from day 1 to day 22, day 1 to day 29, or day 1 to day 36, then every 3 weeks from day 43 until end of treatment visit, up to 38 months)
- Dose escalation：total clearance(PK will be assessed from day 1 to day 22, day 1 to day 29, or day 1 to day 36, then every 3 weeks from day 43 until end of treatment visit, up to 38 months)
- Dose escalation： Plasma ERY974 concentrations(PK will be assessed from day 1 to day 22, day 1 to day 29, or day 1 to day 36, then every 3 weeks from day 43 until end of treatment visit, up to 38 months)
- Dose escalation：Area under curve (AUC)(PK will be assessed from day 1 to day 22, day 1 to day 29, or day 1 to day 36, then every 3 weeks from day 43 until end of treatment visit, up to 38 months)
- Dose escalation：volume distribution(PK will be assessed from day 1 to day 22, day 1 to day 29, or day 1 to day 36, then every 3 weeks from day 43 until end of treatment visit, up to 38 months)
- Dose escalation： Change in tumor size assessed by mRECIST(From the date of informed consents obtained until disease progression: at screening , week 6,12,18 and subsequently every 3 months up to 38 months)
- Dose escalation： Determining the recommended dose(Recommended dose will be determined after completion of DLT assessments in all dose escalation cohorts. It is estimated as 18 months after first patient enrollment.)
- Cohort expansion：Number and severity of adverse events(Adverse events will be reported through 28 days after the last dose)
- Cohort expansion ：Plasma ERY974 concentrations(PK will be assessed from day 1 to day 22, day 1 to day 29, or day 1 to day 36, then every 3 weeks from day 43 until end of treatment visit, up to 38 months)
- Cohort expansion ：Area under curve (AUC)(PK will be assessed from day 1 to day 22, day 1 to day 29, or day 1 to day 36, then every 3 weeks from day 43 until end of treatment visit, up to 38 months)
- Cohort expansion ：terminal half-life(PK will be assessed from day 1 to day 22, day 1 to day 29, or day 1 to day 36, then every 3 weeks from day 43 until end of treatment visit, up to 38 months)
- Cohort expansion ：total clearance(PK will be assessed from day 1 to day 22, day 1 to day 29, or day 1 to day 36, then every 3 weeks from day 43 until end of treatment visit, up to 38 months)
- Cohort expansion ：volume distribution(PK will be assessed from day 1 to day 22, day 1 to day 29, or day 1 to day 36, then every 3 weeks from day 43 until end of treatment visit, up to 38 months)