This study has 2 parts. The first part was open to adults with advanced non-small cell lung cancer. The second part was open also to adults with other types of advanced cancer of the lung, brain, skin, and liver. After early encouraging results, more people with liver cancer can now take part in the study. The participants get a combination of two medicines called BI 836880 and ezabenlimab. BI 836880 is a type of an antibody that blocks new blood vessel formation. New blood vessels are needed by the tumour to continue growing. Ezabenlimab is an antibody that may help the immune system fight cancer (immune checkpoint inhibitor). The purpose of the first part of the study was to find out the highest dose of the BI 836880 that the participants can tolerate in combination with BI 754091. After the best dose of BI 836880 for the combination with ezabenlimab was found, it is used in the second part of the study. The purpose of the second part is to see whether the combination of BI 836880 and BI 754091 is able to make tumours shrink. The participants are in the study as long as they benefit from and can tolerate treatment. During this time, they get infusions of BI 836880 and ezabenlimab every 3 weeks. The doctors also regularly check the general health of the participants.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
252
BI 836880 as an intravenous infusion on day 1 of each 3-week cycle.
240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle.
University of Alabama at Birmingham
Birmingham, Alabama, United States
Beverly Hills Cancer Center
Beverly Hills, California, United States
Winship Cancer Institute
Atlanta, Georgia, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Huntsman Cancer Institute
Salt Lake City, Utah, United States
Part 1 - Number of Patients With Dose Limiting Toxicity (DLT) Within the First Cycle of Treatment
Number of patients with dose limiting toxicity (DLT) within the first cycle of treatment.
Time frame: The first treatment cycle, up to 21 days.
Part 2 - Objective Response (OR)
Objective Response (OR) defined as best overall response (Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)) of complete response (CR) or partial response (PR) from first treatment infusion until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anticancer therapy, lost to follow-up, or withdrawal of consent. In case of recurrent glioblastoma (GBM), assessment will be based on RANO (Response Assessment in Neuro-Oncology) criteria.
Time frame: Up to 778 days.
Part 1 - Adverse Events (AEs)
The number of patients with any adverse events (AEs).
Time frame: Up to 1263 days.
Part 1 - Drug Related AEs
The number of patients with any drug related adverse events (AEs).
Time frame: Up to 1263 days.
Part 1 - Drug Related AEs Leading to Dose Reduction or Discontinuation
The number of patients with any drug related adverse events (AEs) leading to dose reduction or discontinuation.
Time frame: Up to 1263 days.
Part 2 - Adverse Events (AEs)
The number of patients with any adverse events (AEs).
Time frame: Up to 778 days.
Part 2 - Drug Related AEs
The number of patients with any drug related adverse events (AEs).
Time frame: Up to 778 days.
Part 2 - Drug Related AEs Leading to Dose Reduction or Discontinuation
The number of patients with any drug related adverse events (AEs) leading to dose reduction or discontinuation.
Time frame: Up to 778 days.
Part 2 - Disease Control (DC)
Disease control (DC), defined as best overall response of CR, PR, or stable disease (SD) (Response Assessment in Neuro-Oncology (RANO for GBM \& RECIST1.1 for all other cohorts).
Time frame: Up to 778 days.
Part 2 - Duration of Objective Response (DoR)
Duration of objective response (DoR), defined as the time from first documented CR or PR (RANO for GBM \& RECIST1.1 for all other cohorts) until the earliest of disease progression or death among patients with OR.
Time frame: Up to 84.4 weeks.
Part 2 - Progression-free Survival (PFS)
Progression-free survival (PFS) (RANO for GBM \& RECIST1.1 for all other cohorts), defined as the time from first treatment infusion until disease progression or death from any cause, whichever occurs earlier. Tumour shrinkage (in millimeters), defined as the difference between the minimum post-baseline sum of diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) and the baseline sum of diameters of the same set of target lesions in case of RECIST. In GBM, using RANO criteria, tumor shrinkage will be calculated based on the difference between the post-baseline and baseline measurements of the sum of product of the largest bi-dimensional measurements for all target lesions.
Time frame: Up to 778 days.
Part 1 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle
Part 1 - Maximum measured concentration of BI 836880 in plasma (Cmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Part 1 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the Fourth Infusion Cycle
Part 1 - Maximum measured concentration of BI 836880 in plasma (Cmax) after the fourth infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle.
Part 1 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle
Part 1 - Time from dosing to maximum serum concentration of BI 836880 (Tmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Part 1 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the Fourth Infusion Cycle
Part 1 - Time from dosing to maximum serum concentration of BI 836880 (Tmax) after the fourth infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle.
Part 1 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle
Part 1 - Area under the concentration-time curve of BI 836880 in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Part 1 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the Fourth Infusion Cycle
Part 1 - Area under the concentration-time curve of BI 836880 in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the fourth infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle.
Part 2 - Maximum Measured Concentration of BI 836880 in Plasma (Cmax) After the First Infusion Cycle
Part 2 - Maximum measured concentration of BI 836880 in plasma (Cmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Part 2 - Time From Dosing to Maximum Serum Concentration of BI 836880 (Tmax) After the First Infusion Cycle
Part 2 - Time from dosing to maximum serum concentration of BI 836880 (Tmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Part 2 - Area Under the Concentration-time Curve of BI 836880 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle
Part 2 - Area under the concentration-time curve of BI 836880 in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Part 1 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle
Part 1 - Maximum measured concentration of ezabenlimab in plasma (Cmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Part 1 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the Fourth Infusion Cycle
Part 1 - Maximum measured concentration of ezabenlimab in plasma (Cmax) after the fourth infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle.
Part 1 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle
Part 1 - Time from dosing to maximum serum concentration of ezabenlimab (Tmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Part 1 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the Fourth Infusion Cycle
Part 1 - Time from dosing to maximum serum concentration of ezabenlimab (Tmax) after the fourth infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle.
Part 1 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle
Part 1 - Area under the concentration-time curve of ezabenlimab in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Part 1 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the Fourth Infusion Cycle
Part 1 - Area under the concentration-time curve of ezabenlimab in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the fourth infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the fourth cycle.
Part 2 - Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) After the First Infusion Cycle
Part 2 - Maximum measured concentration of ezabenlimab in plasma (Cmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Part 2 - Time From Dosing to Maximum Serum Concentration of Ezabenlimab (Tmax) After the First Infusion Cycle
Part 2 - Time from dosing to maximum serum concentration of ezabenlimab (Tmax) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
Part 2 - Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) After the First Infusion Cycle
Part 2 - Area under the concentration-time curve of ezabenlimab in plasma over the time interval from 0 to 504 hours (AUC0-504h) after the first infusion cycle.
Time frame: 5 minutes before infusion and 1, 2.25, 6, 24, 168, 336 and 504 hours following the end of infusion in the first cycle.
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Virginia Cancer Specialists, PC
Fairfax, Virginia, United States
Royal North Shore Hospital-St Leonards-20807
St Leonards, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
Peninsula & South Eastern Oncology Group
Frankston, Victoria, Australia
Alfred Hospital
Melbourne, Victoria, Australia
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