Description:
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.
Title
- Brief Title: A Study of ERY974 in Patient With Advanced Solid Tumors
- Official Title: A Phase 1 Dose Escalation and Cohort Expansion Study of ERY974, An Anti-Glypican3 (GPC3)/CD3 Bispecific Antibody, in Patients With Advanced Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
ERY101EG
- NCT ID:
NCT02748837
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| ERY974 | | Cohort expansion in esophageal carcinoma |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Dose escalation cohort of ERY974 | Experimental | 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 gastric cancer | Experimental | Patients with GPC3 positive advanced gastric cancer or gastroesophageal junction cancer will receive ERY974 at recommended dose until disease progression. | |
| Cohort expansion in esophageal carcinoma | Experimental | Patients with GPC3 positive advanced squamous cell esophageal carcinoma will receive ERY974 at recommended dose until disease progression. | |
| Cohort expansion in other solid tumors | Experimental | Patients with other GPC3 positive advanced solid tumors will receive ERY974 at recommended dose until disease progression | |
Eligibility Criteria
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Dose escalation： MTD determination |
| Time Frame: | DLT evaluation period, defined as from the first ERY974 injection until 7 days after the third injection |
| Safety Issue: | |
| Description: | Determination of dose-limiting toxicities (DLT) |
Secondary Outcome Measures
| Measure: | Dose escalation： Number and severity of adverse events |
| Time Frame: | Adverse events will be reported through 28 days after the last dose |
| Safety Issue: | |
| Description: | |
| Measure: | Dose escalation： Plasma ERY974 concentrations |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Dose escalation：Area under curve (AUC) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Dose escalation：terminal half-life |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Dose escalation：total clearance |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Dose escalation：volume distribution |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Dose escalation： Change in tumor size assessed by mRECIST |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Dose escalation： Determining the recommended dose |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | |
| Measure: | Cohort expansion：Number and severity of adverse events |
| Time Frame: | Adverse events will be reported through 28 days after the last dose |
| Safety Issue: | |
| Description: | |
| Measure: | Cohort expansion ：Plasma ERY974 concentrations |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Cohort expansion ：Area under curve (AUC) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Cohort expansion ：terminal half-life |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Cohort expansion ：total clearance |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Cohort expansion ：volume distribution |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Chugai Pharmaceutical |
Last Updated
August 22, 2019
