Zipalertinib combo hits PFS endpoint in Phase 3 lung cancer trial

Taiho Oncology, Taiho Pharmaceutical, and Cullinan Therapeutics announced on August 12, 2026 that the Phase 3 REZILIENT3 trial evaluating zipalertinib plus platinum-based chemotherapy versus chemotherapy alone in first-line treatment of adult patients with previously untreated, locally advanced or metastatic non-small cell lung cancer harboring EGFR exon 20 insertion mutations met its primary endpoint of progression-free survival at a planned interim analysis.¹

The companies said the study demonstrated a statistically significant and clinically meaningful improvement in PFS in the zipalertinib containing arm.¹ Observed safety for the zipalertinib containing arm was manageable.¹ Based on these data, the Independent Data Monitoring Committee recommended unblinding the study.¹ The trial will continue to monitor efficacy and safety.¹

Full results from REZILIENT3 will be submitted for presentation at an upcoming international medical conference.¹ Pending discussions with the FDA, the three companies plan to pursue U.S. regulatory approval for the combination regimen in the first-line setting.¹

The trial design: this multicenter, randomized, controlled, open-label global trial enrolled 285 adults with previously untreated, locally advanced or metastatic non-squamous NSCLC with EGFR exon 20 insertion mutations, with the primary objective of assessing progression-free survival in the zipalertinib plus chemotherapy arm versus the chemotherapy arm.¹

Zipalertinib, also known by development code CLN-081/TAS6417, is described as an orally available small molecule designed to target activating mutations in EGFR, designed as a next generation, irreversible EGFR inhibitor for a genetically defined subset of NSCLC patients.¹ The drug remains investigational and has not been approved by any health authority.¹