NB004 + sotorasib

NB004 + sotorasib is a combination therapy being evaluated for the treatment of advanced solid tumors, particularly those harboring KRAS G12C mutations. The combination consists of NB004, a small molecule inhibitor of Src homology region 2 domain-containing phosphatase-2 (SHP2), and sotorasib, a first-in-class small molecule inhibitor of the KRAS G12C mutation. SHP2 is a protein tyrosine phosphatase that acts as a critical signaling node downstream of multiple receptor tyrosine kinases and is essential for the full activation of the RAS/MAPK pathway. By inhibiting SHP2, NB004 aims to block adaptive resistance mechanisms and feedback loops that often reactivate the MAPK pathway during KRAS inhibition. Sotorasib (Lumakras) works by irreversibly binding to the cysteine residue of the inactive GDP-bound KRAS G12C protein, trapping it in an inactive state. The combination is currently in Phase 1 clinical development (e.g., NCT05036291) to assess safety, tolerability, and efficacy in patients who have exhausted standard treatment options.

Other names

NB004 + AMG 510NB-004 + sotorasib