An analysis of LY-3537982's R&D progress and its clinical results presented at the 2024 ASCO_GI Annual Meeting

LY3537982 is an oral, potent, and highly selective inhibitor of GDP-bound KRAS G12C with unique pharmacologic properties that achieve high target occupancy at low absolute exposures. Recently, the clinical results of GI tumors treated on LOXO-RAS-20001, a phase 1 study of LY3537982 in patients (pts) with a KRAS G12C mutation were presented in 2024 ASCO_GI.

LY-3537982's R&D Progress

LY-3537982 is a small molecule drug that targets the KRAS G12C mutation. The therapeutic areas that LY-3537982 aims to address include neoplasms (abnormal growth of cells), respiratory diseases, digestive system disorders, endocrinology and metabolic diseases, and urogenital diseases. This suggests that the drug has the potential to treat a wide range of conditions within these areas.

According to the Patsnap Synapse, LY-3537982 is being developed by Eli Lilly & Co., a pharmaceutical company. The drug is currently in Phase 3 of clinical trials globally. And the clinical trial distributions for LY-3537982 are primarily in the United States, China and United Kingdom. The key indication is Neoplasm Metastasis.

Detailed Clinical Result of LY-3537982

This non-randomized, Sequential Assignment, open-Labelled clinical trial (NCT04956640) was aimed to assess the efficacy and safety of LY3537982 in KRAS G12C-mutant GI cancers.  

In this study, dose escalation followed a mTPI-2 method. Dose expansion included a combination with cetuximab in colorectal cancer (CRC). All pts were KRAS G12C inhibitor naïve. Key objectives were to determine the RP2D, safety, PK, and antitumor activity per RECIST v1.1.

The result showed that as of 24 July 2023, 73 pts with CRC (32), PANC (24), BTC (10), and other GI tumors (7) were treated with 50-200 mg BID LY3537982. Median age was 62 yrs (range, 36-85) and median number of prior lines of therapies was 3 (range, 0-11). No DLTs were observed. Grade 1 diarrhea was the highest frequency TEAE regardless of attribution (33%). At a median time on treatment of 4 months (range, 0.1-18), 20 pts are ongoing and 53 discontinued treatment. In the combination cohort, 46 pts with CRC were treated with 100 or 150 mg BID LY3537982 and cetuximab. Median age was 57 yrs (range, 35-77) and median number of lines of prior therapies was 3 (range, 1-8). 1 pt at 100 mg BID had a DLT (ALT/AST increased) and required a dose reduction. TEAEs ≥30% were dermatitis acneiform (59%), diarrhea (44%), dry skin (44%), hypomagnesemia (33%), and fatigue (30%). Vomiting, pruritus, skin fissures, headache, nausea, pyrexia, and rash were mostly grade 1 with 20-24% occurrence. At a median time on treatment of 6 months (range, 0.6-11), 37 pts are ongoing and 9 discontinued treatment (none due to AE). Table shows efficacy data.

It can be concluded that in pts with GI tumors, LY3537982 alone or in combination with cetuximab demonstrated preliminary efficacy and a favorable safety profile.

How to Easily View the Clinical Results Using Synapse Database?

If you want to know the other clinical results of popular conferences, please lick on the “Clinical Results” on the homepage of Patsnap Synapse, which provides multi-dimensional screening and filtering of drugs, indications, targets, companies, result evaluation, release date, popular conferences, etc. to help you quickly locate the data you need. 

Select the clinical meeting you are interested in, such as ESMO. In the results, you can quickly locate the data you want to view by indication, phase and drug name. 

A single result clearly shows important information such as registration number, phase, indication, Sponsor/Collaborator, biomarker, Trial number, dosing regimen and more. 

If you would like to view more information about this result, you can go to the result detail page by clicking on the title. 

Above the headings, we provide the original source of the outcome data. The basic information is supplemented with more information beyond the list, such as company, study. design, etc. 

In the important Outcome Measures section, we provide both list and flowchart forms, which are convenient for you to overview the comparison group information and core indicator data. 

Finally, if you need to download these results, you can conveniently check the check boxes on the left side of the list, or directly click the "Export" button to download the data for personalized analysis and file sharing.

Click on the image below to embark on a brand new journey of drug discovery!