Benjamin Besse

KRAS inhibitors in NSCLC:
-G12Di: coming soon to meet a major unmet need — same activity in smokers vs never-smokers?
-G12Ci: expanding field, active in both naïve and post-sotorasib/adagrasib pts.
Excellent summary @GarridoLagunaMD #ESMO25

ALEX final OS:
- crizo arm dragged down by <50% getting next-gen ALK. Lack of crossover really hurts.
- 5-yr OS with alectinib ≈ 5-yr PFS with lorlatinib (CROWN), but only 18% got lorla post alect — we still don’t know the optimal sequence. #ESMO25

Is MET IHC predictive of amivantamab efficacy?
Chrysalis-2 in EGFRmut NSCLC post-osimertinib (biopsy at resistance).
Cohorts D&E: ami+lazertinib | Cohort F: ami monotherapy.
ORR higher with MET+, but also seen in MET–.
#WCLC25

Be ready to screen MTAP loss in all pts with advanced NSCLC, regardless of driver.
@mihaela_aldea shows incidence, highest in ALK/RET/EGFR/ROS1.
AMG193 paved the way at #ESMO24.
BMS-986504 confirms druggability: 29% ORR + many durable SD (slide @CharuAggarwalMD). #WCLC25

EGFR update
7 potential options:
•3rd gen TKI: osimertinib, lazertinib, aumolertinib
•Amivantamab
•Pemetrexed
•Carboplatin
•Ivonescimab
•Dato-DXd
OS data favor combos upfront—but real-world ≠ trial. In RWD, ~40% of newly diagnosed pts wouldn’t qualify for FLAURA2 #WCLC25