Clinical trial NCT02748837: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Chugai Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2016-04-22
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Dose escalation： MTD determination
timeFrame: DLT evaluation period, defined as from the first ERY974 injection until 7 days after the third injection
measure: Cohort expansion：Preliminary assessment of change in tumor size
timeFrame: 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 outcomes:
measure: Dose escalation： Number and severity of adverse events
timeFrame: Adverse events will be reported through 28 days after the last dose
measure: Dose escalation： Plasma ERY974 concentrations
timeFrame: 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
measure: Dose escalation：Area under curve (AUC)
timeFrame: 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
measure: Dose escalation：terminal half-life
timeFrame: 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
measure: Dose escalation：total clearance
timeFrame: 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
measure: Dose escalation：volume distribution
timeFrame: 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
measure: Dose escalation： Change in tumor size assessed by mRECIST
timeFrame: 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
measure: Dose escalation： Determining the recommended dose
timeFrame: 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.
measure: Cohort expansion：Number and severity of adverse events
timeFrame: Adverse events will be reported through 28 days after the last dose
measure: Cohort expansion ：Plasma ERY974 concentrations
timeFrame: 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
measure: Cohort expansion ：Area under curve (AUC)
timeFrame: 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
measure: Cohort expansion ：terminal half-life
timeFrame: 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
measure: Cohort expansion ：total clearance
timeFrame: 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
measure: Cohort expansion ：volume distribution
timeFrame: 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
Other outcomes:
Locations:
city: Washington
country: United States
state: District of Columbia
city: Tampa
country: United States
state: Florida
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: New York
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Providence
country: United States
state: Rhode Island
city: Paris
country: France
city: Villejuif
country: France
city: Groningen
country: Netherlands
Study officials:
affiliation: clinical-trials@chugai-pharm.co.jp
name: Sponsor Chugai Pharmaceutical Co. Ltd
role: STUDY_DIRECTOR
References: