Dr Stephen Liu Discusses the CRESTONE Study

Efficacy of Seribantumab in Patients With Advanced Solid Tumors and an NRG1 Gene Fusion

The Clinical study of REsponse to Seribantumab in TumOrs with NEuregulin 1 (NRG1) fusions, or CRESTONE, is a single arm phase 2 study exploring the anti-tumor activity and tolerability of seribantumab in patients with advanced solid tumors and an NRG1 gene fusion. 

The science behind the CRESTONE study details how unregulated activation of HER3 by NRG1 fusion proteins can cause a normal cell to transform into a tumor cell. Though they are rare, NRG1 fusions are found across many solid tumor types. Examples of tumor types that have identified NRG1 fusions include, but not limited to, lung, head and neck, breast, kidney, colorectal, and pancreatic cancers, and cholangiocarcinoma.

Inhibition of the over-activation of HER3 with a targeted HER3 inhibitor like seribantumab may represent a more defined treatment for tumors driven by an NRG1 fusion.

Eligible patients for the CRESTONE study include those with advanced cancer who have not responded or are no longer responding to treatment. Seribantumab has demonstrated acceptable safety and pharmacokinetics in prior clinical testing including over 800 patients to date. Currently, the CRESTONE study is being conducted with registrational intent following an accelerated approval pathway.

This study is open and enrolling patients around the world, including clinical sites in the US, Australia, Canada and South Korea.

Sources:

CRESTONE for Physicians. CRESTONE. Accessed August 23, 2022. https://nrg1fusion.com/physicians/

NRG1 Fusions: The science behind the CRESTONE study. ELEVATION Oncology. Accessed August 23, 2022. https://nrg1fusion.com/wp-content/uploads/2020/07/EO0003-001-000_NRG1-fusion-1-pager.pdf