Announcement • 1h
Taiho Oncology, Inc., Taiho Pharmaceutical Co., Ltd., and Cullinan Therapeutics, Inc. Report Zipalertinib Plus Chemotherapy Meets Primary Endpoint in Phase 3 Rezilient3 Trial in First-Line Egfr Exon 20 Insertion Mutation Non-Small Cell Lung Cancer Taiho Oncology, Inc., Taiho Pharmaceutical Co. Ltd., and Cullinan Therapeutics, Inc. announced that the REZILIENT3 trial, a global Phase 3 clinical trial evaluating the combination of zipalertinib and platinum-based chemotherapy compared with chemotherapy alone in the first-line treatment of adult patients with previously untreated, locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations, met its primary endpoint of progression-free survival (PFS) at a planned interim analysis. In this analysis, the study demonstrated a statistically significant and clinically meaningful improvement in PFS in the zipalertinib containing arm. Observed safety for the zipalertinib containing arm was manageable. Based on these data, the Independent Data Monitoring Committee recommended unblinding the study. The trial will continue to monitor efficacy and safety. Full results from REZILIENT3 will be submitted for presentation at an upcoming international medical conference. Based on these results, pending discussions with the U.S. Food and Drug Administration (FDA), Taiho Oncology, Taiho Pharmaceutical and Cullinan Therapeutics plan to pursue U.S. regulatory approval for this combination regimen in the first-line setting. 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. The primary objective of this trial is to assess progression-free survival in the zipalertinib plus chemotherapy arm versus the chemotherapy arm. Zipalertinib (development code: CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was selected because of its ability to inhibit EGFR variants with exon 20 insertion mutations. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer. Zipalertinib is investigational and has not been approved by any health authority. Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co. Ltd., and in collaboration with Cullinan Therapeutics, Inc. in the U.S. NSCLC is a common form of lung cancer and up to 4% of all cases globally have EGFR ex20ins. In the United States, approximately 16% of patients with NSCLC harbor EGFR mutations, with insertions at exon 20 accounting for up to 12% of these mutations. Live News • Aug 08
Cullinan Therapeutics Advances CLN-049 to Phase 2 After FDA Feedback in AML Cullinan Therapeutics said it is advancing its bispecific T cell engager CLN-049 for acute myeloid leukemia after receiving FDA feedback and has started planning a potentially registrational Phase 2 trial.
The company framed this as a key clinical milestone in its broader pipeline of bispecific T cell engagers, which also includes CLN-978, Velinotamig, and Zipalertinib targeting autoimmune diseases and cancers.
Cullinan Therapeutics shares trade at US$17.73, with the stock up 75.2% year to date, reflecting a strong recent run into this latest development.
Progress on CLN-049 moves Cullinan Therapeutics further into later-stage development, which tends to bring higher trial costs along with clearer data catalysts. The investor focus now shifts to trial design, patient population and timing of initial Phase 2 readouts, since those elements will shape both execution risk and how the rest of the pipeline is funded and prioritized. Announcement • Jul 28
Cullinan Therapeutics Announces Positive End-Of-Phase 1 Meeting With FDA For CLN-049 And Advances Program To A Potentially Registrational Phase 2 Study In AML Cullinan Therapeutics, Inc. received positive feedback from the U.S. Food and Drug Administration (FDA) following an End-of-Phase 1 (EOP1) meeting for CLN-049, a FLT3xCD3 T cell engager being evaluated in patients with acute myeloid leukemia (AML). The EOP1 meeting focused on the planned Phase 2 development strategy for CLN-049. Based on discussions with the FDA, Cullinan will initiate a potentially registrational Phase 2 study of CLN-049 in patients with relapsed/refractory AML in the third quarter of 2026. The study design agreed with the FDA incorporates a short dose-optimization phase with seamless progression to a single-arm cohort at the recommended Phase 2 dose. As presented at the 2025 American Society of Hematology (ASH) Annual Meeting, CLN-049 demonstrated promising clinical activity and a favorable safety profile in patients with relapsed/refractory AML. The Company plans to share an update from the dose escalation portion of this study in Fourth Quarter 2026. Following the positive feedback from the FDA, the Company plans to initiate a potentially registrational Phase 2 study in patients with relapsed/refractory AML in Third Quarter 2026. The Company will also initiate a Phase 1/2 study evaluating the combination of CLN-049, venetoclax, and azacitidine in patients with previously untreated AML (NCT07722767). CLN-049 is a novel, investigational FLT3xCD3 bispecific T cell engager. CLN-049 is designed to target FLT3-expressing leukemia cells, offering a new immunotherapeutic approach for treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). CLN-049 binds to both mutated and non-mutated FLT3, allowing targeted action regardless of FLT3 mutational status, making the investigational treatment widely applicable to a broad population. CLN-049 is being studied in a Phase 1, open-label, multicenter, first-in-human, multiple ascending dose study evaluating safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of intravenously (IV) administered CLN-049 in patients with relapsed/refractory AML or MDS (NCT05143996) and in a parallel Phase 1, open-label, dose escalation and dose expansion study for the treatment of patients with AML with measurable residual disease (MRD) (EUCT 2023-506572-27-00). CLN-049 has received Orphan Drug designation and Fast Track designation from the U.S. FDA for the treatment of relapsed/refractory AML. 
