Dr. Haniel Araujo(@_hanielaraujo )@MDAndersonNews outlined phase 1 results for zoldonrasib, an oral covalent RAS(ON)-G12D inhibitor: ORR 61 % in KRAS G12D NSCLC at the 1200 mg QD RP2D; median time-to-response 1.4 mo and mostly grade 1 AEs. RMC-LUNG-101 expansion is now enrolling.

Excited to share our new study @Nature. Very grateful for the support of our collaborators, pharma and biotech partners and members of the Skoulidis and Heymach labs. Special thanks to star fellow @_hanielaraujo and @minhtruongdo. Thankful to our patients. @MDAndersonNews

A mucinous transcriptional program supports long-term tumor cell persistence to RAS inhibitors and mucinous histological features may predict poor resposme to KRAS G12C inhibitors. These important findings provide new insights for drug development targeting KRAS-mutant NSCLC.

Thrilled to share our findings on the efficacy of the novel RAS(ON) multi-selective inhibitor RMC-7977 in difficult-to-treat KRASG12C mutant NSCLC and mechanisms of tolerance to RAS inhibition. Check our paper in Cancer Discovery! https://t.co/zomSt9llu5 @CD_AACR @MDAndersonNews

@HCCvPDAC Lastly, @_hanielaraujo, @XimoPechuan, Teng Zhou, @FSkoulidis, et al show in NSCLC the RAS(ON) multiselective inhibitor RMC-7977 is active in KRASG12C-mut models resistant to G12C inhibitors, but a mucinous txtn state supports drug tolerance https://t.co/tGy2qPrUPs @MDAndersonNews

https://t.co/g9nVeGdo7k

https://t.co/6kXoVSeFaQ

Really glad to be co-first author in this important work presented at #AACR23 and published in Cancer Discovery. Congratulations to all authors from 21 centers in US and Europe! Co-mutations and #KRAS G12C Inhibitor Efficacy in Advanced NSCLC @MDAndersonNews @OncoAlert @CD_AACR

@LucasUratani @pires_veridiana @BraghiroliIgnez @GilbertodeCas13 @paulohoff10 @pilarestevezmd @rdtiecher

We hypothesize that the negative effect of PPI/ATB could be caused by gut microbiome dysbiosis. Take home message: pay attention to what you prescribe immediately prior/during IO treatment!

Regarding the use of ATB/PPI along w/ IO: concomitant PPI was associated with lower OS/PFS, while fortunately ATB did not seem to affect efficacy.

In line w/ recent literature, our data suggest that they can: among 216 pts. from our institution, prior use of ATB or PPI (<60 days from the beginning of IO) was associated with lower OS and PFS, even after multivariate analyses.

Our abstract at #ASCO21! Immunotherapy depends on a functioning cancer-immunity cycle to work. Can the use of ATB or proton pump inhibitors (PPI) disrupt the cycle enough to dampen IO efficacy?