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

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BAY94-9343

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tyuo, Japan, 104-0045
    • National Cancer Center Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BAY94-9343; Cohort 1: Safety, tolerability and PK of 4.5 mg/kg dose given Q3W. Proceeding to Cohort 2 or not will be decided based on both safety variables during Cycle 1 (21 days) of 3 to 6 subjects in Cohort 1 and PK obtained from Cycle 1 (at least Day 1 to Day 5). Cohort 2: Safety, tolerability and PK of 6.5 mg/kg dose given Q3W. Whether recruitment will be continued up to 9 subjects for Cohort 2 or not will be decided based on safety variables during Cycle 1 (21 days) of the first 3 subjects in Cohort 2. The safety and tolerability of 6.5 mg/kg will be assessed based on the data of 9 subjects during Cycle 1 in Cohort 2, and considering long term toxicity, the safety and tolerability of BAY94-9343 will be assessed all safety data by the end of 3 cycles in Cohort 2.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Treatment-emergent Adverse Events (TEAEs) as a measure of safety and tolerability	Up to 9 weeks
Intensity of TEAEs acc. to NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) v.4.03	Up to 9 weeks
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)
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)
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)
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)
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)
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)
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 Outcome Measures

Outcome Measure	Time Frame
Tumor response based on RECIST (Response Evaluation Criteria in Solid Tumors)	Up to 9 weeks
Level of mesothelin expression using IHC (Immunohistochemistry) staining for the tumor tissue obtained from fresh or archival tumor tissue	Up to 9 weeks
Plasma levels of soluble mesothelin	Up to 9 weeks
Immunogenicity evaluation based on anti-BAY94-9343 antibody count	Up to 9 weeks

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2015
• Primary Completion (Actual): April 28, 2017
• Study Completion (Actual): July 4, 2017

Study Registration Dates

• First Submitted: June 26, 2015
• First Submitted That Met QC Criteria: June 26, 2015
• First Posted (Estimate): June 30, 2015

Study Record Updates

• Last Update Posted (Actual): June 4, 2018
• Last Update Submitted That Met QC Criteria: June 1, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Phase I; Japan; endometrial; mesothelin; Advanced, refractory solid tumors; solid cancers; adenocarcinoma of lung; BAY 94-9343; Anetumab ravtansine; ADC (Antibody Drug Conjugate); gastrointestinal, ovarian, pancreatic, cholangio, mesothelioma and triple negative breast cancers
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 15404

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No