ESMO Congress 2026

Sotorasib (AMG510) is a small-molecule inhibitor that selectively and irreversibly targets KRAS G12C, a mutation found in about 13% of non-small-cell lung cancers (NSCLC) and 1% to 3% of colorectal cancers and other tumors ^[2]. The evidence chain for this asset is well established: a phase 1 trial enrolled 129 patients with advanced solid tumors (59 NSCLC, 42 colorectal cancer, 28 other tumors), with no dose-limiting toxic effects or treatment-related deaths, and a confirmed objective response rate of 32.2% (19 patients) in the NSCLC subgroup ^[2]; a single-group phase 2 trial treated 126 previously treated patients with KRAS p.G12C-mutated advanced NSCLC at 960 mg once daily, 81.0% of whom had received both platinum-based chemotherapy and PD-1 or PD-L1 inhibitors ^[1]; and a randomized, open-label phase 3 trial compared sotorasib with docetaxel at 148 centres in 22 countries in KRASG12C-mutated advanced NSCLC progressing after platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor ^[5]. Sotorasib is also an approved directly KRAS G12C-targeted drug in clinical use ^[4].

At this meeting (posts tagged #ESMO26 and #LCSM), the only news directly related to sotorasib consists of two posts: @Tony_Calles wrote 'Bye bye sotorasib', and @Rtsugitom wrote 'A much larger difference than anticipated!'. Neither post disclosed the trial name, comparator, endpoint or any figures, nor any abstract or presentation source; the underlying data remain undisclosed or to be confirmed. On their face, the messages convey a farewell to sotorasib and a difference far larger than expected, but which readout they refer to cannot be verified from the posts.

Against existing knowledge, sotorasib's position rests on phase 3 evidence versus docetaxel ^[5], while resistance biology suggests that position is not unchallenged: in an analysis of resistance to adagrasib monotherapy, putative resistance mechanisms were detected in 17 of 38 patients (45%), including secondary KRAS alterations (G12D/R/V/W, G13D, Q61H, R68S, H95D/Q/R, Y96C and high-level amplification of the KRASG12C allele) plus bypass mechanisms such as MET amplification and alterations in NRAS, BRAF, MAP2K1 and RET ^[3]; a case report also documented polyclonal resistance converging on RAS-MAPK reactivation ^[6]. In this context, if the 'much larger difference' hinted at in the posts involves a comparison within the same drug class, it would be a test against a higher bar than ^[5], with sotorasib as the reference; but the posts name neither the comparators nor any figures, so this step forward currently rests only on the wording of the posts.

The limitations are straightforward: everything tied to this meeting comes from two social media posts, with no verifiable efficacy or safety figures or trial identifiers; the numbers cited from the background literature are previously published results and cannot be extrapolated to this meeting's readout. Any judgment on sotorasib's competitive position should wait for formal data disclosure.