*January 2025*
Key Takeaways
- Zipalertinib demonstrated a 40% ORR and 90% DCR in NSCLC patients with EGFR exon 20 insertion mutations, meeting the trial’s primary endpoint.
- Patients previously treated with amivantamab showed a higher ORR of 50%, indicating potential efficacy in this subgroup.
- Common treatment-related adverse effects included rash, paronychia, and anemia, with grade 3 or higher events being less frequent.
- Regulatory submission for zipalertinib in the United States is planned for the second half of 2025, pending FDA discussions.
The phase 1/2 REZILIENT1 trial (NCT04036682), which is examining the novel EGFR TKI zipalertinib (CLN-081) in patients with non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations, has met its primary end point of overall response rate (ORR), according to phase 2b findings from the study.1 Moreover, the safety profile of the agent was generally consistent with what was reported in prior data presentations.
At a data cutoff of March 29, 2024, prior findings from phase 2b of REZILIENT1 presented during the 2024 ESMO Congress demonstrated that efficacy-evaluable patients who received zipalertinib (n = 30) achieved a confirmed ORR of 40.0% (95% CI, 22.7%-59.4%), including a 3.3% (95% CI, 0.1%-17.2%) complete response (CR) rate; the disease control rate (DCR) was 90.0% (95% CI, 73.5%-97.9%).2 The median duration of response (DOR) was not estimable (NE), and the median progression-free survival (PFS) was 9.7 months (90% CI, 4.1-NE).
Evaluable patients who received prior amivantamab-vmjw (Rybrevant) only (n = 18) experienced a confirmed ORR of 50.0% (95% CI, 26.0%-74.0%), with a CR rate of 5.6% (95% CI, 0.1%-27.3%) and a DCR of 88.9% (95% CI, 65.3%-98.6%). Evaluable patients who received prior amivantamab and other exon 20 insertion–directed agents (n = 12) achieved a confirmed ORR of 25.0% (95% CI, 5.5%-57.2%) and a DCR of 91.7% (95% CI, 61.5%-99.8%). Read more.
