A Study of ERY974 in Patient With Advanced Solid Tumors

A Phase 1 Dose Escalation and Cohort Expansion Study of ERY974, An Anti-Glypican3 (GPC3)/CD3 Bispecific Antibody, in Patients With Advanced Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: ERY974

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France
  • Villejuif, France
• Netherlands
  • Groningen, Netherlands
• United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Tampa, Florida, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Michigan
    • Detroit, Michigan, United States
  • New York
    • New York, New York, United States
  • North Carolina
    • Durham, North Carolina, United States
  • Rhode Island
    • Providence, Rhode Island, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: ERY974
Experimental: 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.	Drug: ERY974
Experimental: Cohort expansion in esophageal carcinoma; Patients with GPC3 positive advanced squamous cell esophageal carcinoma will receive ERY974 at recommended dose until disease progression.	Drug: ERY974
Experimental: Cohort expansion in other solid tumors; Patients with other GPC3 positive advanced solid tumors will receive ERY974 at recommended dose until disease progression	Drug: ERY974

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose escalation： MTD determination	Determination of dose-limiting toxicities (DLT)	DLT evaluation period, defined as from the first ERY974 injection until 7 days after the third injection
Cohort expansion：Preliminary assessment of change in tumor size	Anti-tumor activity will be assessed by modified Response Evaluation Criteria in Solid Tumors (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

Secondary Outcome Measures

Outcome Measure	Time Frame
Dose escalation： Number and severity of adverse events	Adverse events will be reported through 28 days after the last dose
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：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： 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

Collaborators and Investigators

• Sponsor: Chugai Pharmaceutical
• Investigators: Study Director: Sponsor Chugai Pharmaceutical Co. Ltd, clinical-trials@chugai-pharm.co.jp

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Actual): August 1, 2019
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: March 29, 2016
• First Submitted That Met QC Criteria: April 20, 2016
• First Posted (Estimate): April 22, 2016

Study Record Updates

• Last Update Posted (Actual): August 22, 2019
• Last Update Submitted That Met QC Criteria: August 21, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ERY101EG