calaspargase pegol-mknl + cobimetinib

This combination therapy consists of **calaspargase pegol-mknl** (Asparlas), a pegylated L-asparaginase, and **cobimetinib** (Cotellic), a small molecule MEK inhibitor. Calaspargase pegol-mknl is a biologic enzyme that depletes systemic levels of the amino acid L-asparagine by converting it into aspartic acid and ammonia. This starves cancer cells, such as those in pancreatic ductal adenocarcinoma (PDAC), which are often auxotrophic for asparagine due to low levels of asparagine synthetase (ASNS). Cobimetinib targets the MAPK/ERK signaling pathway by inhibiting MEK1 and MEK2. The rationale for this combination is based on preclinical findings that RAS/MAPK signaling can compensate for asparaginase-induced metabolic stress; thus, dual inhibition of asparagine availability and MEK signaling is intended to synergistically induce tumor cell death. This regimen is currently being evaluated in the Phase I CASPER trial led by the OHSU Knight Cancer Institute for patients with locally advanced or metastatic pancreatic cancer.

Other names

Calaspargase pegol-mknl and cobimetinibAsparlas and CotellicCASPER trial combination