P3, N=160, Active, not recruiting, Amgen | Trial completion date: Jan 2026 --> May 2026

Here, we show that the KRAS G12C inhibitor LY3499446 induces CIN in KRAS -mutant NSCLC cell lines...In the presence of Aurora Kinase A inhibition, cyclin B1 stabilization delays mitotic exit and diverts cell fate from mitotic slippage or division toward mitotic catastrophe. Together, our findings identify CIN as a predictive marker of response to combined KRAS G12C and Aurora Kinase A inhibition, providing mechanistic rationale to enhance the therapeutic window of AURKA inhibitors when used with targeted therapies.

P1/2, N=74, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: May 2026 --> Nov 2026 | Trial primary completion date: Apr 2026 --> Oct 2026

These results identify the PD-L1-driven immunosuppressive microenvironment as a key mediator of sotorasib resistance and propose PD-L1i as a synergistic strategy to overcome resistance, which warrants clinical exploration of sequential or combinatorial regimens.

Compared with positive control MRTX849, the synthesized compounds 7g, 7p, 7q, 7r, 7v, and 7y displayed stronger antiproliferative activities against H358 cells with IC50 values of < 1 nM (3D cell culture) and comparable inhibitory potency against KRASG12C...Meaningfully, 7q combined with Nrf2 inhibitor ML385 or PARP7 inhibitor RBN-2397 greatly enhanced the sensitivity of 7q against lung cells (H1373) in vivo. Furthermore, combination therapy of 7q with pan-USP inhibitor PR-619 obtained a statistically significant synergistic inhibition of H1373 cell growth in vitro and in vivo. Our findings indicate that 7q may be a promising drug candidate for the treatment of cancers harboring the KRASG12C mutation, and the results of the combination regimen established a pharmacological foundation for addressing drug resistance.

P1, N=18, Not yet recruiting, M.D. Anderson Cancer Center

P2, N=14, Recruiting, Amgen | Not yet recruiting --> Recruiting

P2, N=10, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Mar 2027 --> Jan 2026 | Trial primary completion date: Mar 2027 --> Jan 2026

P1/2, N=257, Recruiting, Sichuan Huiyu Pharmaceutical Co., Ltd | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

CXCL1/CXCR2 and HGF/c-MET may represent compensatory pathways that sustain proliferation and survival in resistance to KRASG12C inhibitors. The simultaneous blockade of these signals may offer a novel strategy for bypassing resistance.

P2, N=68, Active, not recruiting, ETOP IBCSG Partners Foundation | Trial primary completion date: Dec 2025 --> Jul 2025

In addition, rivaroxaban and sotorasib were well tolerated by the healthy subjects. These results suggest that rivaroxaban can be safely co-administered without the need for switching to another treatment or dose adjustments in patients treated with sotorasib.