Clinical trial NCT02485119: Phase I Dose Escalation Study of BAY94-9343 Given by Intravenous Infusion Every 3 Weeks in Japanese Subjects With Advanced Malignancies
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: BAY 94-9343
Anetumab ravtansine
ADC (Antibody Drug Conjugate)
Phase I
Japan
solid cancers
Advanced, refractory solid tumors
mesothelin
endometrial
adenocarcinoma of lung
gastrointestinal, ovarian, pancreatic, cholangio, mesothelioma and triple negative breast cancers
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-06-30
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Treatment-emergent Adverse Events (TEAEs) as a measure of safety and tolerability
timeFrame: Up to 9 weeks
measure: Intensity of TEAEs acc. to NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) v.4.03
timeFrame: Up to 9 weeks
measure: Cmax (maximum drug concentration in plasma after single dose administration ) for BAY94-9343, total antibody compound, DM4, metabolite DM4-Me
timeFrame: 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)
measure: Cmax,norm (Cmax divided by dose (mg) per kg body weight) for BAY94-9343, total antibody compound, DM4, metabolite DM4-Me
timeFrame: 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)
measure: Cmax/D (Cmax divided by dose (mg)) for BAY94-9343, total antibody compound, DM4, metabolite DM4-Me
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: AUC(0-tlast)/D (AUC(0-tlast) divided by dose (mg)) for BAY94-9343, total antibody compound, DM4, metabolite DM4-Me
timeFrame: 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)
measure: tmax (time to reach maximum drug concentration in plasma) for BAY94-9343, total antibody compound, DM4, metabolite DM4-Me
timeFrame: 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 outcomes:
measure: Tumor response based on RECIST (Response Evaluation Criteria in Solid Tumors)
timeFrame: Up to 9 weeks
measure: Level of mesothelin expression using IHC (Immunohistochemistry) staining for the tumor tissue obtained from fresh or archival tumor tissue
timeFrame: Up to 9 weeks
measure: Plasma levels of soluble mesothelin
timeFrame: Up to 9 weeks
measure: Immunogenicity evaluation based on anti-BAY94-9343 antibody count
timeFrame: Up to 9 weeks
Other outcomes:
Locations:
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Tyuo
country: Japan
facility: National Cancer Center Hospital
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: