KRAS G12C inhibitor

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BI 1823911: a KRAS G12C Inhibitor

BI 1823911* is a highly potent and selective inhibitor targeting KRAS G12C mutations, which interferes with signalling, blocking proliferation, and causes tumor cell apoptosis.1

Clinical trials: BI 1823911 currently being investigated in a Phase I trial involving patients with advanced or metastatic solid tumours expressing the KRAS G12C mutation.2

Role of KRAS

KRAS functions as a molecular switch, intrinsically linked to and controlled by GTP-(‘on’) or GDP-(‘off’) binding. Its function is at the center of various signaling pathways, including the RAS-RAF-MEK-ERK cascade, which regulate several different processes including cell proliferation and survival.1

About BI 1823911

Mechanism of action

BI 1823911 selectively and covalently binds to G12C mutant KRAS, irreversibly locking it in its inactive GDP form, thereby interfering with signalling, blocking proliferation, and causing tumor cell apoptosis.1

BI 1823911 mechanism of action
ERK, extracellular signal-regulated kinases; GDP, guanosine diphosphate; GTP, guanosine triphosphate; KRAS, Kirsten rat sarcoma; MEK, mitogen-activated protein kinase; SOS1, Son of sevenless homolog 1.

Combination Therapy

Monotherapy with a KRAS G12C inhibitor may not be sufficient to achieve durable responses, whereas combination therapy may lead to enhanced anti-tumor efficacy and may address resistance mechanisms as well.3

Preclinical data identified strong synergistic anti-proliferative activity with BI 1701963, a pan-KRAS SOS1 inhibitor, and this combination will be tested in future studies.3,4

 

Clinical Development

Initial data from in vivo and in vitro studies have shown that BI 1823911 showed promising anti-tumor responses against KRAS-dependent tumors, especially when given in combination with BI 1701963, a pan-KRAS SOS1 inhibitor.3 The combination showed increased and sustained pharmacodynamic modulation and deeper anti-tumor efficacy.3,4 A study is currently underway investigating the efficacy of BI 1823911 alone and in combination with BI 1701963 in advanced or metastatic cancers including lung cancer, colorectal cancer, pancreatic cancer, and bile duct cancer.2

More information about Boehringer Ingelheim oncology clinical trials can be found on the MyStudyWindow website. Relevant trials for the KRAS G12C inhibitor include: BI 1472-0001.

 

KRAS G12C inhibitor clinical trials

KRAS, Kirsten rat sarcoma.
Trial number Phase Treatment Patient population Status

NCT04973163 (1472.1)2

I

BI 1823911 as monotherapy and in combination with BI 1701963

Advanced or metastatic solid tumors expressing KRAS G12C mutation

Recruiting

Explore our latest KRAS G12C inhibitor data

Our latest data on the KRAS G12C inhibitor was presented at the American Association for Cancer Research Congress 2021.

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References

1

Boehringer Ingelheim, data on file.

2

ClinicalTrials.gov. NCT04973163. https://clinicaltrials.gov/ct2/show/NCT04973163 (Accessed: September 2021).

3

Savarese F et al. Poster presented at the American Association for Cancer Research Congress 2021.

4

Hofmann MH et al. Poster presented at the American Association for Cancer Research Congress 2021.

*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.

 

© 2021 Boehringer Ingelheim International GmbH. All rights reserved.

 

Page last updated: September 2021