Novartis releases positive early clinical data for unique KRASG12C inhibitor at AACR

Swiss pharm giant Novartis (NOVN: VX) has announced promising clinical data for JDQ443, an investigational selective, covalent, and orally bioavailable KRASG12C inhibitor at the annual meeting of American Association for Cancer Research (AACR). Comprehensive information on the discovery of JDQ443 is also included in a poster being presented today with further details published in the journal Cancer Discovery.

Preliminary data (Phase Ib/II) from the KontRASt-01 study (NCT04699188) showed that JDQ443, discovered at Novartis, demonstrated anti-tumor activity, high systemic exposure at its recommended dose, and a favorable safety profile based on initial clinical data in patients with KRAS G12C-mutated solid tumors. The data were submitted as a late-breaking abstract and will be presented today in an oral session.

KRAS mutations are the most frequent oncogenic drivers in NSCLC, the most common type of lung cancer. The most common form of KRAS mutation is G12C. JDQ443 inhibits this mutated form of KRAS in a structurally distinct way, trapping KRAS G12C in a GDP-bound, inactive state while avoiding direct interaction with H95, a recognized route for resistance. In pre-clinical models, JDQ443 potently inhibited KRAS G12C cellular signalling and proliferation in a mutant-selective manner and demonstrated dose-dependent antitumor activity.

Phase III anticipated mid-2022