The purpose of this study is to evaluate: * The side effects of BAY1129980 when given every 21 days different dose levels. * Determine the dose level of BAY1129980 that should be tested in future clinical research studies. * Measure how much BAY1129980 is in the blood at specific times after administration. * If treatment with BAY1129980 shows any effect on reducing the tumor growth. * If there are specific biomarkers that might be able to explain why some patients respond to treatment and others do not. * If treatment with BAY1129980 causes an immune response from the body against the drug (immunogenicity).
The relatively restricted C4.4a expression pattern provides a target for the selective delivery of a cytotoxic drug to C4.4.a-expressing tumor cells by means of a suitable antibody-drug conjugate. The subject population eligible for the current study will be those subjects with advanced malignancies known to express C4.4a, which are refractory to standard therapy or those without standard therapy or actively refusing any treatment, which would be regarded as standard and in whom, in the opinion of the investigator, experimental therapy with BAY1129980 may be beneficial.Depending on the number of dose-escalating steps and the occurrence of DLTs, the planned numbers of subjects could vary.It is expected that up to 90 subjects may participate in the dose-expansion phase of the study and up to 6-9 subjects may particpate in the dose re-esclation phase.The study assessments in the expansion phase of the study are identical to those in the dose-escalation phase. Amendment # 3 includes changes to DLT criteria (hematological and non-hematological) and allows for frequent follow-up for subjects experiencing drug-related liver toxicity that warrants dose reduction or dose interruptions.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
69
Starting dose is 0.15mg/kg intravenous (I.V.) administration every 21 days.
Unnamed facility
La Jolla, California, United States
Unnamed facility
Stanford, California, United States
Unnamed facility
Aurora, Colorado, United States
Maximum tolerated dose (MTD)
MTD is defined as the maximum dose at which the incidence of DLTs (dose limiting toxicities) during Cycle 1 is below 20%, or the maximum dose administered, whichever is achieved first during dose escalation.
Time frame: 21 days
Number of participants with adverse events as a measure of safety and tolerability
Time frame: Up to 2 years
C4.4a expression levels in tumour tissue as measured by immunohistochemistry (IHC)
Time frame: Baseline
Tumor response evaluation following RECIST 1.1 criteria
Time frame: Up to 2 years
Plasma concentration of BAY1129980 characterized by AUC (0-tlast)
Time frame: 2 years
Antidrug and antibody titer
Time frame: Baseline and up to 2 years
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Unnamed facility
Washington D.C., District of Columbia, United States
Unnamed facility
Gainesville, Georgia, United States
Unnamed facility
Westwood, Kansas, United States
Unnamed facility
Hackensack, New Jersey, United States
Unnamed facility
Buffalo, New York, United States
Unnamed facility
New York, New York, United States
Unnamed facility
Durham, North Carolina, United States
...and 5 more locations