This study is open to adults with different types of advanced or metastatic cancer (including lung cancer, colorectal cancer, pancreatic cancer, and bile duct cancer). This study is for people for whom previous treatment was not successful or no treatment exists. People who have a tumour with a KRAS mutation can participate in the study. A KRAS mutation makes tumours grow faster. BI 1823911 and BI 1701963 are medicines that may turn off KRAS, each in a different way. In this study, BI 1823911 is given to people for the first time. The purpose of this study is to find the highest dose of BI 1823911 that people can tolerate when taken alone and together with BI 1701963. The most suitable dose is used to find out whether BI 1823911 alone and in combination with BI 1701963 can make tumours shrink. Participants can stay in the study as long as they benefit from treatment and can tolerate it. During this time, participants take tablets of BI 1823911 alone or in combination with BI 1701963 once a day. The doctors regularly monitor the size of the tumour. Doctors also regularly record any unwanted effects and check participant's health.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
BI 1823911
BI 1701963
Midazolam - only administered in Part B (dose confirmation) of the Monotherapy Arm
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Sarah Cannon Research Institute at Mary Crowley
Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Brussels - HOSP Jules Bordet
Anderlecht/Brussels-Capital, Belgium
Edegem - UNIV UZ Antwerpen
Edegem/Antwerpen, Belgium
Universitair Ziekenhuis Gent
Gent/Oost-Vlaanderen, Belgium
UZ Leuven
Leuven/Vlaams-Brabant, Belgium
Hospital Universitari Vall D Hebron
Barcelona, Spain
The Christie
Manchester, United Kingdom
Dose escalation (Part A) - Monotherapy and combination therapy: Number of patients experiencing Dose limiting toxicities (DLTs) during the Maximum tolerated dose (MTD) evaluation period for BI 1823911 in monotherapy and in each combination
DLTs are graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: up to 28 days
Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Objective response (OR) defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR)
BOR is determined according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. BOR will consider all tumour assessments from first treatment administration until the earliest of disease progression, death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent.
Time frame: up to 39 months
Dose escalation (Part A) - Monotherapy and combination therapy: Number of patients experiencing DLTs during all treatment cycles for BI 1823911 in monotherapy and in each combination
Time frame: up to 39 months
Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Objective response (OR)
OR is defined as best overall response (BOR) of complete response (CR) or partial response (PR), both regardless of confirmation. BOR is determined according to RECIST version 1.1. BOR will consider all tumour assessments from first treatment administration until the earliest of disease progression, death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent.
Time frame: up to 39 months
Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Duration of OR
Duration of OR is defined as the time from first documented CR or PR until disease progression or death (whichever occurs first) among patients with OR.
Time frame: up to 39 months
Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Tumour shrinkage (in millimetres)
Tumour shrinkage is 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 longest diameters of the same set of target lesions.
Time frame: up to 39 months
Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Progression-free survival (PFS) rate
PFS is defined as the time from first treatment administration until tumour progression according to RECIST version 1.1 or death from any cause, whichever occurs earlier.
Time frame: at month 6
All study parts: Number of patients with adverse events during the on-treatment period
Time frame: up to 39 months
All study parts, BI 1823911: Maximum concentration (Cmax)
Time frame: up to 24 hours
All study parts, BI 1823911: Steady state concentration (Css)
Time frame: up to 24 hours
All study parts, BI 1823911: Area under the plasma concentration-time curve from time zero to time t (AUCτ)
Time frame: up to 24 hours
All study parts, BI 1823911: Area under the plasma concentration-time curve at steady state (AUCss)
Time frame: up to 24 hours
All study parts, BI 1701963: Maximum concentration (Cmax)
Time frame: up to 24 hours
All study parts, BI 1701963: Steady state concentration (Css)
Time frame: up to 24 hours
All study parts, BI 1701963: Area under the plasma concentration-time curve from time zero to time t (AUCτ)
Time frame: up to 24 hours
All study parts, BI 1701963: Area under the plasma concentration-time curve at steady state (AUCss)
Time frame: up to 24 hours
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.