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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Bayer
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT02485119
First received: June 26, 2015
Last updated: March 16, 2017
Last verified: March 2017
  Purpose

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.


Condition Intervention Phase
Neoplasms
Drug: BAY94-9343
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Number of Treatment-emergent Adverse Events (TEAEs) as a measure of safety and tolerability [ Time Frame: Up to 9 weeks ]
  • Intensity of TEAEs acc. to NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) v.4.03 [ Time Frame: Up to 9 weeks ]
  • Cmax (maximum drug concentration in plasma after single dose administration ) for BAY94-9343, total antibody compound, DM4, metabolite DM4-Me [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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:
  • Tumor response based on RECIST (Response Evaluation Criteria in Solid Tumors) [ Time Frame: Up to 9 weeks ]
  • Level of mesothelin expression using IHC (Immunohistochemistry) staining for the tumor tissue obtained from fresh or archival tumor tissue [ Time Frame: Up to 9 weeks ]
  • Plasma levels of soluble mesothelin [ Time Frame: Up to 9 weeks ]
  • Immunogenicity evaluation based on anti-BAY94-9343 antibody count [ Time Frame: Up to 9 weeks ]

Estimated Enrollment: 15
Actual Study Start Date: August 14, 2015
Estimated Study Completion Date: May 11, 2018
Estimated Primary Completion Date: May 15, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02485119

Contacts
Contact: Bayer Clinical Trials Contact clinical-trials-contact@bayerhealthcare.com

Locations
Japan
Recruiting
Kashiwa, Chiba, Japan, 277-8577
Recruiting
Tyuo, Japan, 104-0045
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02485119     History of Changes
Other Study ID Numbers: 15404
Study First Received: June 26, 2015
Last Updated: March 16, 2017

Keywords provided by Bayer:
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

Additional relevant MeSH terms:
Maytansine
Immunoconjugates
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 26, 2017