P1/2, N=294, Recruiting, Jacobio Pharmaceuticals Co., Ltd. | Not yet recruiting --> Recruiting

P1, N=240, Recruiting, Treeline Biosciences, Inc.

The anticancer activities of SS-3091 and SS-30125 have been validated against the KRas G12D, G12C, G12V, and G12S mutants in various cancer cells. All findings underscore the potential of SS-3091 and SS-30125 as very promising active pan-KRas inhibitors.

Here, we comprehensively evaluated the preclinical efficacy of BI-2493, a first-in-class allele-agnostic mutant-KRAS inhibitor (panKRASi), in pancreatic ductal adenocarcinoma (PDAC)...In the long term, emergence of resistance to panKRASi monotherapy was associated with increased YAP signaling within tumor cells and enhanced expression of immune checkpoints in the TME that impede effective T cell function. Our multifaceted approach identified potential combinatorial approaches for generating sustained responses to panKRASi.

P1, N=434, Recruiting, Amgen | Not yet recruiting --> Recruiting

MCB-294 also demonstrates superior activity compared to the inactive-state selective pan-KRAS inhibitor Bl-2865 and the KRASG12D inhibitor MRTX1133...Notably, both MCB-294 and MCB-36 effectively suppress KRASG12C inhibitor-resistant cancer cells and remodel the tumor immune microenvironment. These findings highlight a promising therapeutic strategy for broadly targeting KRAS-driven tumors and overcoming drug resistance.

P1, N=200, Recruiting, Erasca, Inc. | Not yet recruiting --> Recruiting

P1, N=434, Not yet recruiting, Amgen

Spirocyclization led to the discovery of BI-2493, a highly rigid analogue exhibiting better potency, metabolic stability, and permeability. BI-2493 shows in vivo efficacy in various KRAS mutant and KRAS wild-type amplified xenograft models and represents a promising starting point for further optimization.

P1, N=514, Recruiting, BeiGene | N=177 --> 514

P1, N=200, Not yet recruiting, Erasca, Inc.

P1/2, N=294, Not yet recruiting, Jacobio Pharmaceuticals Co., Ltd.