Abstract CT048: A Phase II trial of JDQ443 in KRAS G12C- mutated NSCLC with PD-L1 expression <1% or PD-L1 expression≥1% and an STK11 co-mutation

Background Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most frequently mutated oncogene in non-small cell lung cancer (NSCLC). KRAS G12C, the most frequent KRAS variant, is found in ~13% of patients (pts) with NSCLC. KRAS is a GTPase that regulates cell signaling pathways necessary for proliferation, differentiation, and survival. KRAS mutation reduces the intrinsic GTPase activity of the enzyme, allowing for the accumulation of active, GTP-bound KRAS and hyperactivation of downstream signaling, driving tumorigenesis. JDQ443 is a potent, selective KRASG12C inhibitor that irreversibly traps KRASG12C in its inactive, GDP bound state and blocks downstream signaling. In preliminary data from the Phase Ib part of the KontRASt-01 study (NCT04699188), JDQ443 showed promising antitumor activity and an acceptable safety profile in previously treated pts with KRAS G12C-mutated advanced NSCLC. Pts with KRAS G12C-mutated NSCLC currently receive the same first-line (1L) treatment as those without driver mutations, consisting of immunotherapy alone or combined with chemotherapy; however, ~30% of pts with NSCLC present with programmed death-ligand 1 (PD-L1) expression