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

Study Overview
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Brief Summary
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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

Official Title
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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.

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: BAY1179470


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Dose escalation, Advanced, refractory solid tumors, FGFR2