Cullinan Therapeutics, Inc. announced positive initial data in patients receiving zipalertinib after prior treatment with amivantamab enrolled in its pivotal Phase 2b REZILIENT1 clinical trial. As of a January 12, 2024 data cut-off, 31 patients had been enrolled. Patients had received a median of three prior systemic anti-cancer regimens, including prior platinum-based chemotherapy, prior anti-PD1/L1 therapy, and prior epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy.

Zipalertinib has a unique chemical structure that is distinct from other exon20 insertion directed agents, which makes it highly selective for mutant exon 20 versus wild-type EGFR. Cullinan entered into a partnership with Taiho in 2022, with an upfront cash payment of $275M and additional payments totaling $130M to be made for US regulatory approvals in 1L and 2L+ NSCLC. Cullinan also retains a 50/50 profit share in the U.S. Cullinan and Taiho have a broad development program for zipalertinib through a suite of REZILIENT studies, including two ongoing pivotal studies in 1L and 2L+ exon20 insertion NSCLC as well as studies in other patient populations such as patients with active brain metastases and those with uncommon EGFR mutations.

Both Module B2 (post chemo only) and Module C (post approved ex20ins treatments) of the pivotal REZILIENT1 trial remain on track to complete enrollment by end of 2024, consistent with prior projections. Zipalertinib (CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was engineered to inhibit EGFR variants with exon 20 insertion mutations, while sparing wild-type EGFR.

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 has received Breakthrough Therapy Designation from the FDA. Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co.

Ltd., and Cullinan Therapeutics, Inc.Cullinan Pearl Corp., which Taiho Pharmaceutical Co. Ltd., acquired from Cullinan Therapeutics, Inc. in 2022, previously licensed the rights to zipalertinib in Greater China to Zai Lab Limited in 2020.