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Erasca to Study ERK Inhibitor With Pfizer's Ibrance in Tumors Harboring KRAS, NRAS Mutations

NEW YORK – Erasca and Pfizer on Thursday announced a clinical trial collaboration and supply agreement to study the ERK1/2 inhibitor ERAS-007 in combination with Pfizer's Ibrance (palbociclib) in KRAS- and NRAS-mutant cancers.

The firms have agreed to conduct a proof-of-concept study of the drug combination in patients with KRAS- and NRAS-mutant colorectal cancer and KRAS-mutant pancreatic cancer. Erasca is sponsoring the trial, and Pfizer is providing Ibrance at no cost.

Erasca and Pfizer are already collaborating on the Phase Ib/II HERKULES-3 trial. In that study, researchers are exploring the ERAS-007-Ibrance combination and a triple combination of ERAS-007, Pfizer's BRAF inhibitor Braftovi (encorafenib), and Eli Lilly's EGFR inhibitor Erbitux (cetuximab) in patients with metastatic colorectal cancer harboring mutations in BRAF V600E, KRAS, or NRAS.

San Diego-based Erasca is also studying ERAS-007 as a monotherapy in advanced solid tumors, and as a combination therapy in patients with EGFR-mutant and KRAS G12C-mutant non-small cell lung cancer.

The biological rationale for the latest trial has support in preclinical data showing the synergistic anti-tumor effect of RAS/MAPK pathway and cell cycle inhibition in colorectal cancer and pancreatic tumors. "ERAS-007 blocks RAS/MAPK pathway signaling at the terminal node with robust inhibitory activity across RAS mutations, while data support palbociclib inhibition of CDK4/6 leading to cell cycle arrest," Erasca CEO Jonathan Lim said in a statement. "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."