News: Erasca Reorganizes and Deprioritizes Development of ERAS-801 for rGBM
Yet Another EGFR-targeted Monotherapy Drops Anchor
After the markets closed yesterday, Erasca (Nasdaq: ERAS) announced that it has undertaken a significant corporate reorganization with the in-licensing of some new development candidates focused on cancers driven by the RAS/MAPK pathway, an 18% workforce reduction and the deprioritization of company-sponsored clinical development of ERAS-801 for rGBM.
This sort of move happens all the time in small Biopharma companies that have a modest Balance Sheet, and thus, must continuously review investment allocation decisions as new data becomes available. However, the deprioritization of ERAS-801 is noteworthy for the brain cancer community.
MissionGBM View: As we have written/spoken/shouted many times both on this website and during our speaking engagements at public brain cancer conferences (see here and here and the reference linked therein), a monotherapy targeted at EGFR in GBM/HGGs is not a winning strategy. Yes, a fair number of HGGs display copy number amplification of EGFR (as well as other oncogenes), but the gene tends to be resident on ecDNA cassettes. When one introduces an EGFR blocker, the cancer cells rapidly react by modulating the expression of EGFR from ecDNA, thus removing the target and abolishing the mode of therapeutic action. Because HGGs are heterogenous, the net result is that the cancer cells that do not display EGFR gain a competitive advantage, and the tumor progresses with little overall impact from the therapy.
Bottom Line: We advise any Sponsors that are developing an EGFR-targeted monotherapy for GBM/HGGs to either (a) STOP right away and reallocate your precious investment capital; or (b) pair the EGFRi with another non-EGFR therapeutic agent in a more effective combination protocol.
Stayed Tuned: In an upcoming episode of “Brain Cancer Science Talk”, we will be speaking with Paul Mischel, MD (Stanford) about ecDNA, its role in cancer neoplastic transformation and some potential strategies for how to more effectively treat cancers that are driven by oncogenes resident on ecDNA.
IMPORTANT NOTE FOR NEURO-ONCOLOGISTS: Please carefully consider administering osimertinib (Tagrisso®) to your patients who have previously been receiving anti-PD(L)-1 immunotherapy. Some of the worst irSAEs that we have ever seen occurred when the published clinical literature in this regard has been ignored (see here). It is bad enough that an EGFRi is not going to provide much therapeutic benefit in GBM/HGG, but to subject a patient to horrendous and unnecessary irSAEs as a consequence of treatment must be avoided.