LY3499446

P1/2, N=5, Terminated, Eli Lilly and Company | N=230 --> 5 | Trial completion date: Dec 2021 --> Oct 2020 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2021 --> Oct 2020; The study was terminated due to an unexpected toxicity finding.

P1/2, N=230, Active, not recruiting, Eli Lilly and Company | Recruiting --> Active, not recruiting

P1/2, N=230, Recruiting, Eli Lilly and Company | Suspended --> Recruiting

EGFR inhibitors improved the degree of target engagement achieved by LY3499446 and this was also associated with enhanced anti-tumor activity in vitro and in vivo. Based on these data, LY3499446 is being tested with abemaciclib, erlotinib, and cetuximab in a Phase I clinical study (NCT94165031).

P1/2, N=230, Suspended, Eli Lilly and Company | Recruiting --> Suspended

Both AMG 510 from Amgen and MRTX849 from Mirati Therapeutics covalently binds to KRAS at the cysteine at residue 12, keeping KRAS in its inactive GDP-bound state and inhibiting KRAS-dependent signaling...In addition, two novel KRAS G12C inhibitors JNJ-74699157 and LY3499446 will have entered phase 1 studies by the end of 2019. Given the rapid clinical development of 4 direct covalent KRAS G12C inhibitors within a short period of time, understanding the similarities and differences among these will be important to determine the best treatment option based on tumor specific response (NSCLC versus colorectal carcinoma), potential resistance mechanisms (i.e. anticipated acquired mutation at the cysteine 12 residue) and central nervous system (CNS) activity. Additionally, further investigation evaluating the efficacy and safety of combination therapies with agents such as immune checkpoint inhibitors will be important next steps.

P1/2, N=230, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting