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

NCT02485119 | Completed Phase 1

• 1 other identifier: 15404
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (4)

• 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

Study Arms (1)

BAY94-9343

EXPERIMENTAL

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

Interventions

BAY94-9343 DRUG

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.

BAY94-9343

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (2)

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

National Cancer Center Hospital

Tyuo, 104-0045, Japan

Location

MeSH Terms

Conditions

Neoplasms; Adenocarcinoma of Lung; Mesothelioma; Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Adenoma; Neoplasms, Mesothelial; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2015
• First Posted: June 30, 2015
• Study Start: August 14, 2015
• Primary Completion: April 28, 2017
• Study Completion: July 4, 2017
• Last Updated: June 4, 2018

Record last verified: 2018-05

Locations

JP (2)