HRS-4642

P2, N=20, Not yet recruiting, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

P2, N=49, Not yet recruiting, Shanghai Zhongshan Hospital

P2, N=20, Not yet recruiting, Ruijin Hospital

P1/2, N=70, Enrolling by invitation, Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting --> Enrolling by invitation

P2, N=120, Not yet recruiting, Fudan University

P1/2, N=35, Recruiting, Fudan University | Not yet recruiting --> Recruiting

P1/2, N=118, Not yet recruiting, Jiangsu HengRui Medicine Co., Ltd.

describe a novel KRASG12D inhibitor, HRS-4642, that shows potent and selective anti-tumor activity across various models and synergizes with proteasome inhibitors. Responses have also been observed in patients during an ongoing phase 1 trial.

Additionally, HRS-4642, either as a single agent or in combination with carfilzomib, reshaped the tumor microenvironment toward an immune-permissive one. In summary, this study provides potential therapies for patients with KRAS G12D-mutant cancers, for whom effective treatments are currently lacking.

P1/2, N=35, Not yet recruiting, Fudan University

P1/2, N=70, Not yet recruiting, Jiangsu HengRui Medicine Co., Ltd.

Preliminary results from phase I trials respectively evaluating RMC-6236, a pan-RAS inhibitor, and HRS-4642, a KRASG12D inhibitor, indicate that both are safe and show promising signs of antitumor activity. These are just two of the candidate RAS therapies in a burgeoning development space as the field looks ahead to drugs that hit more than just KRASG12C.

Conclusions HRS-4642 showed a tolerable safety profile and preliminary anti-tumor activity in advanced solid tumors harboring KRAS G12D mutation. Dose escalation is ongoing and expected to proceed to dose expansion soon.

P1, N=108, Recruiting, Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting --> Recruiting

P1, N=108, Not yet recruiting, Jiangsu HengRui Medicine Co., Ltd.