Cullinan Therapeutics Shares Positive Phase 2b Zipalertinib Data at ESMO 2024

Cullinan Therapeutics, Inc., a biopharmaceutical company listed on Nasdaq as CGEM, has announced updated data from its pivotal Phase 2b REZILIENT1 clinical trial. This trial involves patients with non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) exon 20 insertion mutations and have previously been treated with amivantamab. The findings were presented at the European Society for Medical Oncology Congress 2024.

As of the data cut-off on March 29, 2024, the trial had enrolled 45 patients. These patients had undergone a median of three prior anti-cancer treatments, including platinum-based chemotherapy, anti-PD1/L1 therapy, and EGFR tyrosine kinase inhibitor (TKI) therapy, in addition to amivantamab.

Out of the 30 patients evaluated for response, 1 patient (3%) achieved a complete response (CR), 11 patients (37%) showed a partial response (PR), and 15 patients (50%) had stable disease (SD). The objective response rate (ORR) was consistent with results observed in the Phase 1/2a part of the study, in which patients received zipalertinib after prior chemotherapy.

The safety profile of zipalertinib was manageable and consistent with previous reports. The most common treatment-related adverse events in more than 10% of patients included rash (38%), paronychia (36%), anemia (24%), dry skin (20%), dermatitis acneiform (16%), nausea (16%), and stomatitis (11%). Most of these adverse events were of grade 1 or 2 severity, and there were no grade 4 or 5 treatment-related adverse events.

Dr. Jeffrey Jones, Chief Medical Officer of Cullinan Therapeutics, expressed satisfaction with the updated data, highlighting the potential of zipalertinib for heavily pre-treated EGFR ex20ins mutation NSCLC patients who have progressed after amivantamab treatment. He noted that the completion of the Phase 2b trial enrollment ahead of schedule bolsters their confidence in the drug's potential.

Dr. Antonio Passaro from the European Institute of Oncology highlighted that this is the first presentation to systematically characterize the anti-tumor activity of zipalertinib in heavily treated patients with advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations, who have received prior amivantamab. He emphasized the drug's promising efficacy and manageable safety profile in addressing a significant unmet medical need.

Zipalertinib features a unique chemical structure that makes it highly selective for mutant exon 20 compared to wild-type EGFR. Cullinan and Taiho are conducting a comprehensive development program for zipalertinib through various REZILIENT studies, which include ongoing pivotal studies in first-line and second-line NSCLC with ex20ins mutations, as well as studies targeting other patient populations, such as those with active brain metastases and rare EGFR mutations.

Cullinan entered into a partnership with Taiho in 2022, receiving an upfront payment of $275 million, with the potential for additional payments totaling $130 million upon achieving U.S. regulatory milestones. Cullinan retains a 50/50 profit share in the U.S.

Zipalertinib (CLN-081/TAS6417) is an orally available small molecule specifically designed to target activating mutations in EGFR, particularly exon 20 insertion mutations, while sparing wild-type EGFR. The drug is engineered as a next-generation, irreversible EGFR inhibitor for treating a genetically defined subset of NSCLC patients. It has received Breakthrough Therapy Designation from the U.S. FDA.

Zipalertinib is being developed collaboratively by Taiho Oncology, Inc., Taiho Pharmaceutical Co., Ltd., and Cullinan Therapeutics, Inc. In 2022, Cullinan Pearl Corp., acquired by Taiho Pharmaceutical Co., Ltd., previously licensed the rights to zipalertinib in Greater China to Zai Lab Limited in 2020.

Cullinan Therapeutics, Inc. is committed to developing new standards of care for patients, with a diverse portfolio of clinical-stage assets aimed at inhibiting key disease drivers or harnessing the immune system to eliminate diseased cells in autoimmune diseases and cancer. Anchored in oncology, immunology, and translational medicine, Cullinan aims to create transformative therapeutics by identifying appropriate targets and selecting optimal modalities for development.