HRS-4642 + SHR-A1921

**HRS-4642 + SHR-A1921** is a combination therapy comprising a **KRAS G12D inhibitor** (HRS-4642) and a **TROP-2-targeted antibody-drug conjugate (ADC)** (SHR-A1921). HRS-4642 is a potent, selective, and non-covalent inhibitor designed to target KRAS G12D, a prevalent oncogenic mutation in various solid tumors, especially pancreatic, colorectal, and lung cancers. It inhibits KRAS G12D-mediated signaling, suppresses MEK and ERK phosphorylation, and alters the tumor microenvironment towards an immune-permissive state[3][5]. SHR-A1921 is an ADC targeting **trophoblast cell-surface antigen 2 (TROP-2)**, delivering cytotoxic payloads specifically to TROP-2-expressing cancer cells, and has shown activity in non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), platinum-resistant ovarian cancer, and advanced salivary gland cancer[2]. Combination studies are ongoing in advanced solid tumors with KRAS G12D mutations, aiming to enhance antitumor efficacy by co-targeting oncogenic signaling and surface antigen-mediated cytotoxicity[1][2].