This is a study in adults with advanced cancer (solid tumours) in whom previous chemotherapy was not successful. Only people who have a tumour with a KRAS mutation can participate in the study. A KRAS mutation makes cancer grow faster. The study tests 2 medicines called BI 1701963 and trametinib. BI 1701963 prevents reactivation of KRAS. In this study, BI 1701963 is given to humans for the first time. Trametinib is an approved medicine (MEK inhibitor). The purpose of this study is to find out the highest dose of BI 1701963 alone and in combination with trametinib the participants can tolerate. Another purpose is to check whether BI 1701963 in combination with trametinib is able to make tumours shrink. Participants can stay in the study as long as they benefit from treatment and can tolerate it. During this time, they get tablets of BI 1701963 and trametinib once daily. The doctors regularly monitor the size of the tumour. Doctors also regularly record any unwanted effects and check participants' health.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
71
Tablet
Tablet
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
Sarah Cannon Research Institute-Nashville-48456
Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Universitätsklinikum Köln (AöR)
Cologne, Germany
Universitätsklinikum Frankfurt
Frankfurt am Main, Germany
Erasmus Medisch Centrum-ROTTERDAM-50697
Rotterdam, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, Netherlands
Dose escalation (Part A) - Maximum tolerated dose (MTD) based on number of dose-limiting toxicities (DLTs)
Time frame: 4 weeks
Dose confirmation (Part B) - Number of patients with DLTs during the on-treatment period
Time frame: Up to 3 years
Dose confirmation (Part B) and expansion (Part C) - Objective response
Time frame: Up to 3 years
Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of BI 1701963: Cmax (maximum measured concentration of the analyte in plasma)
Time frame: Up to 5 weeks
Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of BI 1701963: AUCτ (area under the concentration-time curve over a uniform dosing interval τ)
Time frame: Up to 5 weeks
Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of trametinib: Cmax (maximum measured concentration of the analyte in plasma)
Time frame: Up to 5 weeks
Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of trametinib: AUCτ (area under the concentration-time curve over a uniform dosing interval τ)
Time frame: Up to 5 weeks
Dose confirmation (Part B) - Pharmacokinetic parameters of BI 1701963: Cmax (maximum measured concentration of the analyte in plasma)
Time frame: Up to 5 weeks
Dose confirmation (Part B) - Pharmacokinetic parameters of BI 1701963: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)
Time frame: Up to 5 weeks
Dose confirmation (Part B) - Pharmacokinetic parameters of midazolam: Cmax (maximum measured concentration of the analyte in plasma)
Time frame: Up to 5 weeks
Dose confirmation (Part B) - Pharmacokinetic parameters of midazolam: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)
Time frame: Up to 5 weeks
Dose confirmation (Part B) - Number of patients with Grade ≥3 treatment-related adverse events observed during the on-treatment period
Time frame: Up to 3 years
Dose confirmation (Part B) and expansion (Part C) - Duration of Objective response (OR)
Time frame: Up to 3 years
Dose confirmation (Part B) and expansion (Part C) - Tumour shrinkage (in millimetres)
Time frame: Up to 3 years
Dose confirmation (Part B) and expansion (Part C) - Progression-free survival
Time frame: 6 months
Dose confirmation (Part B) and expansion (Part C) - Number of patients with Grade ≥3 treatment-related adverse events observed during the on-treatment period
Time frame: Up to 3 years
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