RMC-4630 + cobimetinib

RMC-4630 is an oral, selective inhibitor of SHP2 (Src homology 2 domain-containing phosphatase 2), a key node in the RAS signaling pathway. Cobimetinib is an oral MEK inhibitor, approved for use in combination with vemurafenib for BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma. The combination of RMC-4630 and cobimetinib targets both upstream (SHP2) and downstream (MEK) components of the oncogenic RAS signaling cascade, aiming to provide synergistic anti-tumor effects in patients with relapsed/refractory solid tumors harboring specific genomic mutations such as KRAS mutations/amplifications, BRAF Class 3 mutations, or NF1 LOF mutations[1][2][9]. This approach is designed to overcome adaptive resistance seen with single-agent therapy. The combination has shown enhanced anti-tumor activity in preclinical models and is being evaluated clinically for safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy[1][2].

Brand names

Cotellic