Zipalertinib: Enhanced Accessibility & Quality of Life in NSCLC
Helena Yu, MD, discusses the importance of zipalertinib's oral administration route for patients with EGFRm non–small cell lung cancer.
Helena Yu, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, highlighted key advantages of new treatments like zipalertinib, an oral EGFR inhibitor, for patients with EGFR exon 20 insertion (ex20ins) mutations.
"I think it's absolutely increasing accessibility and quality of life for patients," Yu stated. She contrasted it with existing options like subcutaneous amivantamab (Rybrevant), which, despite its convenience, still requires regular clinic visits. More importantly, she emphasized the difference in adverse effect profiles.
"Amivantamab, while very effective, has significant EGFR and MET-directed side effects, including notable rates of rash, paronychia, and edema, which can be limiting for some patients."
There is a critical need, especially for older or frail patients, for effective drugs with a more favorable toxicity profile. Yu explained that zipalertinib offers "much more EGFR mutant-specific capabilities and is more potent, so you don't need really high doses that have a lot of EGFR wild-type toxicity. You're really focusing on target inhibition, which I think is ideal for patients."
The immediate goal for this registrational phase 2 REZILIENT1 study (NCT04036682) is to secure accelerated FDA approval for zipalertinib. Beyond that, an exciting future avenue is exploring its use in the first-line treatment setting.
"The REZILIENT3 study [NCT05973773] is ongoing, looking at chemotherapy vs chemotherapy plus zipalertinib as first-line treatment," Yu noted. She added, "When we find something active, our next goal is, can we move it up in the lines of sequencing?" The results of REZILIENT3 will serve as the confirmatory study should zipalertinib receive accelerated approval.
