First-in-man Dose Escalation Study of BAY1179470 in Patients With Advanced, Refractory Solid Tumors

An Open-label, Phase I, Dose-escalation Study to Characterize the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous BAY 1179470 in Subjects With Advanced, Refractory Solid Tumors.

An open-label, non-randomized, Phase I dose-escalation study designed to assess the safety, tolerability, pharmacokinetics(PK) /pharmacodynamics( PD) and tumor response profile of BAY1179470 in subjects with advanced, refractory solid tumors

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BAY1179470

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 811-1395
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
  • Saitama
    • Kita-Adachigun, Saitama, Japan, 362-0806
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
    • Koto-ku, Tokyo, Japan, 135-8550
• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
• Singapore
  • Singapore, Singapore, 119074
  • Singapore, Singapore, 169610

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:

• Subjects with advanced, histologically or cytologically confirmed solid tumors refractory to any standard therapy or have no standard therapy available or subjects actively refuse any treatment which would be regarded standard
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 and a life expectancy of at least 3 months
• Adequate bone marrow, liver, and renal function.

For subjects in the additional cohort:

• Subjects with advanced, histologically or cytologically confirmed gastric cancer.
• At least moderate FGFR2 expression in the tumor tissue from archival samples is confirmed

Exclusion Criteria:

• History of severe allergic reactions to monoclonal antibody therapy
• Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 90 mmHg, despite optimal medical management
• Any condition that is unstable or could jeopardize the safety of the subject and his / her compliance in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAY1179470 (Dose escalation); BAY1179470 will be administered as a 1-hour intravenous infusion every 21 days.	Drug: BAY1179470; BAY1179470 will be administered as a 1-hour intravenous infusion.
Experimental: BAY1179470 (additional); Additional cohort: BAY1179470 will be administered as a 1-hour intravenous infusion every 21 days.	Drug: BAY1179470; BAY1179470 will be administered as a 1-hour intravenous infusion.
Experimental: BAY1179470 (expansion); Expansion cohort: BAY1179470 will be administered as a 1-hour intravenous infusion every 21 days.	Drug: BAY1179470; BAY1179470 will be administered as a 1-hour intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with Adverse Events as a Measure of Safety and Tolerability	Up to 2 years
Maximum drug concentration versus time curve (AUC) from zero to infinity after single (first) and multiple doses of BAY1179470	Cycle 1 and 2: pre-dose, 0.5, 1 , 2, 3, 5, 8, 24, 48, 72, 168 and 336 hours after start of the infusion, Cycle 3 and 4: pre-dose and 1 hour after start of the infusion; each cycle is 21 days
Maximum drug concentration (Cmax) and minimal drug concentration (Cmin) of BAY1179470 in plasma after single and multiple dose administration	Cycle 1 and 2: pre-dose, 0.5, 1 , 2, 3, 5, 8, 24, 48, 72, 168 and 336 hours after start of the infusion, Cycle 3 and 4: pre-dose and 1 hour after start of the infusion; each cycle is 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response	Tumor response will be evaluated based on the RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria.	Every 42 days
Biomarker (plasma)		Cycle 1: pre-dose, 24 hours after start of the infusion and Day 15, Cycle 2, 3 and 4: pre-dose; each cycle is 21 days
Biomarker (biopsy)	Additional cohort only	Cycle 1: pre-dose and Day 8; cycle 1 is 21 days
Immunogenicity	Analyzed for anti-BAY 1179470 antibodies	Cycle 1 and Cycle 2 pre-dose and every second cycle thereafter pre-dose. End of treatment visit and follow-up visit up to 2 years; each cycle is 21 days

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2013
• Primary Completion (Actual): March 18, 2016
• Study Completion (Actual): August 16, 2016

Study Registration Dates

• First Submitted: June 17, 2013
• First Submitted That Met QC Criteria: June 17, 2013
• First Posted (Estimate): June 19, 2013

Study Record Updates

• Last Update Posted (Actual): September 14, 2017
• Last Update Submitted That Met QC Criteria: September 13, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Phase I; Dose escalation; Advanced, refractory solid tumors; FGFR2
• Other Study ID Numbers: 16182