Phase I Dose Escalation Study of BAY94-9343 Given by Intravenous Infusion Every 3 Weeks in Japanese Subjects With Advanced Malignancies

Neoplasms Clinical Trial

Official title:

An Open Label, Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BAY94-9343 Given by Intravenous Infusion Every 3 Weeks (Q3W) in Japanese Subjects With Advanced Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02485119
• Other study ID #: 15404
• Status: Completed
• Phase: Phase 1
• Start date: August 14, 2015
• Est. completion date: July 4, 2017

Study information

• Verified date: May 2018
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objectives of the Phase I study 15404 are to evaluate the safety, tolerability and pharmacokinetics of BAY94-9343 given once every 3 weeks in Japanese subjects with advanced, refractory solid tumors.

The secondary objectives are to investigate the efficacy, biomarkers and immunogenicity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 4, 2017
• Est. primary completion date: April 28, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Japanese subjects = 20 years of age

• ECOG Performance Status of 0 to 1

• Life expectancy of at least 12 weeks

• Subjects with advanced, histologically or cytologically confirmed solid tumors, not amenable to any standard therapy, have no standard therapy available

• Subjects whose fresh or archival tumor tissues are available

• Measurable disease with at least one lesion that can be accurately measured in at least one dimension according to RECIST criteria (Version 1.1 or modified version)

• Adequate bone marrow, liver, and renal function

Exclusion Criteria:

• Anticancer chemotherapy, experimental cancer therapy, or immunotherapy within 2 weeks of start of the first dose

• Impaired cardiac function or clinically significant cardiac disease (i.e., congestive heart failure (CHF) NYHA Class III or IV)

• Myocardial infarction or onset of unstable angina < 3 months prior to general screening

• Cardiac arrhythmias in the electrocardiogram that would interfere with QT/QTc interval measurement (LBBB (left bundle branch block), AV block, atrial fibrillation)

• QTc >470 ms, derived as the average of the 3 values measured by the ECG recorder's algorithm on the ECG triplicate

• LVEF (left ventricular ejection fraction) <50 %

• Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 90 mmHg, despite optimal medical management

• Known human immunodeficiency virus (HIV) infection

• Subjects with an active hepatitis B or C infection requiring treatment

• Personal or family history of Long QT Syndrome (LQTS)

• Subject with clinically significant eye disorders

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• BAY94-9343
Cohort 1: 4.5 mg/kg of BAY 94-9343 at Q3W dose regimen. Cohort 2: 6.5 mg/kg of BAY 94-9343 at Q3W dose regimen.

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	National Cancer Center Hospital	Tyuo

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Treatment-emergent Adverse Events (TEAEs) as a measure of safety and tolerability		Up to 9 weeks
Primary	Intensity of TEAEs acc. to NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) v.4.03		Up to 9 weeks
Primary	Cmax (maximum drug concentration in plasma after single dose administration ) for BAY94-9343, total antibody compound, DM4, metabolite DM4-Me		Cycle 1, 3 ,6: pre, 30, 60min, 1.5, 2, 3, 5, 8, 48, 96, 168 and 504 hours after the start of dosing; Cycle1,2 only: 336 hours; Cycle1 only: 24 hours (each cycle is 21 days)
Primary	Cmax,norm (Cmax divided by dose (mg) per kg body weight) for BAY94-9343, total antibody compound, DM4, metabolite DM4-Me		Cycle 1, 3 ,6: pre, 30, 60min, 1.5, 2, 3, 5, 8, 48, 96, 168 and 504 hours after the start of dosing; Cycle1,2 only: 336 hours; Cycle1 only: 24 hours (each cycle is 21 days)
Primary	Cmax/D (Cmax divided by dose (mg)) for BAY94-9343, total antibody compound, DM4, metabolite DM4-Me		Cycle 1, 3 ,6: pre, 30, 60min, 1.5, 2, 3, 5, 8, 48, 96, 168 and 504 hours after the start of dosing; Cycle1,2 only: 336 hours; Cycle1 only: 24 hours (each cycle is 21 days)
Primary	AUC(0-tlast) (area under the plasma concentration vs time curve from time 0 to the last data point) for BAY94-9343, total antibody compound, DM4, metabolite DM4-Me		Cycle 1, 3 ,6: pre, 30, 60min, 1.5, 2, 3, 5, 8, 48, 96, 168 and 504 hours after the start of dosing; Cycle1,2 only: 336 hours; Cycle1 only: 24 hours (each cycle is 21 days)
Primary	AUC(0-tlast)norm (AUC(0-tlast) divided by dose (mg) per kg body weight) for BAY94-9343, total antibody compound, DM4, metabolite DM4-Me		Cycle 1, 3 ,6: pre, 30, 60min, 1.5, 2, 3, 5, 8, 48, 96, 168 and 504 hours after the start of dosing; Cycle1,2 only: 336 hours; Cycle1 only: 24 hours (each cycle is 21 days)
Primary	AUC(0-tlast)/D (AUC(0-tlast) divided by dose (mg)) for BAY94-9343, total antibody compound, DM4, metabolite DM4-Me		Cycle 1, 3 ,6: pre, 30, 60min, 1.5, 2, 3, 5, 8, 48, 96, 168 and 504 hours after the start of dosing; Cycle1,2 only: 336 hours; Cycle1 only: 24 hours (each cycle is 21 days)
Primary	tmax (time to reach maximum drug concentration in plasma) for BAY94-9343, total antibody compound, DM4, metabolite DM4-Me		Cycle 1, 3 ,6: pre, 30, 60min, 1.5, 2, 3, 5, 8, 48, 96, 168 and 504 hours after the start of dosing; Cycle1,2 only: 336 hours; Cycle1 only: 24 hours (each cycle is 21 days)
Secondary	Tumor response based on RECIST (Response Evaluation Criteria in Solid Tumors)		Up to 9 weeks
Secondary	Level of mesothelin expression using IHC (Immunohistochemistry) staining for the tumor tissue obtained from fresh or archival tumor tissue		Up to 9 weeks
Secondary	Plasma levels of soluble mesothelin		Up to 9 weeks
Secondary	Immunogenicity evaluation based on anti-BAY94-9343 antibody count		Up to 9 weeks

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