A Study of ERY974 in Patient With Advanced Solid Tumors
- Registration Number
- NCT02748837
- Lead Sponsor
- Chugai Pharmaceutical
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 29
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort expansion in gastric cancer ERY974 Patients with GPC3 positive advanced gastric cancer or gastroesophageal junction cancer will receive ERY974 at recommended dose until disease progression. Dose escalation cohort of ERY974 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. Cohort expansion in other solid tumors ERY974 Patients with other GPC3 positive advanced solid tumors will receive ERY974 at recommended dose until disease progression Cohort expansion in esophageal carcinoma ERY974 Patients with GPC3 positive advanced squamous cell esophageal carcinoma will receive ERY974 at recommended dose until disease progression.
- Primary Outcome Measures
Name Time Method Dose escalation： MTD determination 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 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)
- Secondary Outcome Measures
Name Time Method 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：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： 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： 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