Phase 1 CLSP-5282 KRAS G12V–HLA-A03:01 T-cell engager in solid tumors

This Phase 1 open-label, multicenter, dose-escalation and expansion trial (SENTINEL-101) evaluates CLSP-5282 in adults whose advanced/metastatic solid tumors harbor KRAS G12V and who are HLA-A03:01 positive. CLSP-5282 is a first-in-class T-cell engager from Clasp Therapeutics designed to recognize the KRAS G12V mutant peptide presented by HLA-A*03:01 on tumor cells and recruit/activate T cells to kill those cells. Part A uses monotherapy dose escalation to establish safety/tolerability and characterize PK/PD, and Part B expands into indication-specific cohorts (pancreatic adenocarcinoma, colorectal cancer, and non-small cell lung cancer) plus an “all other solid tumors” cohort. The key commercial/scientific angle is “intracellular oncoprotein targeting” via peptide–HLA recognition (rather than a surface antigen), potentially opening an immunotherapy path for KRAS G12V tumors that often lack a direct approved targeted therapy. Today’s care for these refractory populations is still dominated by tumor-type regimens (e.g., chemo backbones in PDAC/CRC, and chemo ± immunotherapy in NSCLC) with limited mutation-specific options for KRAS G12V, so this tests a precision, off-the-shelf immunotherapy approach after standard treatments.