Erasca and Pfizer have entered a clinical trial partnership and supply agreement for palbociclib (Ibrance), an inhibitor of CDK4/6.
Under the collaboration, the companies will conduct a clinical proof-of-concept trial of ERAS-007 plus palbociclib to treat KRAS- and NRAS-mutant colorectal cancer (CRC) and KRAS-mutant pancreatic ductal adenocarcinoma (PDAC).
The combination therapy is being assessed as part of the Phase Ib/II HERKULES-3 master protocol trial underway in gastrointestinal (GI) malignancy patients.
The trial is sponsored by Erasca while Pfizer is delivering palbociclib free of charge.
Erasca chairman, CEO and co-founder Jonathan Lim said: “Preclinical evidence supports synergistic anti-tumour effects when downstream RAS/MAPK pathway inhibition is combined with cell cycle inhibition in CRC and PDAC.
“ERAS-007 blocks RAS/MAPK pathway signalling at the terminal node, with robust inhibitory activity across RAS mutations while data support palbociclib inhibition of CDK4/6 leading to cell cycle arrest.
“Based on their respective mechanisms of action, ERAS-007 and palbociclib offer a promising combination to overcome adaptive resistance in patients with these highly prevalent oncogenic drivers.”
Erasca is evaluating whether hindering ERK1/2, the RAS/MAPK signalling pathway’s terminal node, along with palbociclib could reduce the treatment resistance development and boost therapeutic benefits.
An oral ERK1/2 inhibitor, ERAS-007 is being analysed as a single agent or along with various inhibitors that act on the RAS/MAPK pathway’s upstream nodes as part of the MAPKlamp strategy of Erasca.
Erasca previously entered a similar agreement with Pfizer and Eli Lilly and Company to assess ERAS-007 plus encorafenib and cetuximab.
In September this year, Pfizer and Strata Oncology extended their collaboration for a trial of various cancer therapies in new, biomarker-guided patient groups.