Cullinan Therapeutics Reports Positive Phase 2b REZILIENT1 Study Results for Zipalertinib

Cullinan Therapeutics, Inc., a biopharmaceutical firm listed on Nasdaq under CGEM, has recently reported promising early results from its Phase 2b REZILIENT1 clinical trial involving zipalertinib (CLN-081/TAS6417). This investigational drug is aimed at patients previously treated with amivantamab. The study, which enrolled 31 participants as of January 12, 2024, seeks to evaluate zipalertinib's effectiveness in treating non-small cell lung cancer (NSCLC) with EGFR exon20 insertion mutations.

Patients involved in the trial had undergone a median of three prior systemic anti-cancer treatments, including platinum-based chemotherapy, anti-PD1/L1 therapy, and EGFR tyrosine kinase inhibitors (TKIs). At the data cut-off point, 18 patients were assessed for response. These patients demonstrated anti-tumor activity comparable to those who had only undergone prior chemotherapy in the earlier Phase 1/2a portion of the study.

The results indicated that zipalertinib has a manageable safety profile similar to what has previously been reported, with no grade 4 or grade 5 treatment-related adverse events. "In an evolving treatment landscape, this is the first clinical data to systematically characterize the potential of an irreversible and selective EGFR exon20 insertion mutation TKI such as zipalertinib in heavily pre-treated patients," said Jeffrey Jones, MD, MBA, Chief Medical Officer at Cullinan Therapeutics. Jones added that the initial results are encouraging, particularly given the recent approval of amivantamab in combination with chemotherapy as a first-line treatment.

The safety and efficacy of zipalertinib in a post-amivantamab setting were found to be similar to those in patients who had progressed after platinum-based chemotherapy alone. This strengthens the confidence in zipalertinib's potential to meet a significant unmet need for patients with NSCLC harboring EGFR exon20 insertion mutations.

Zipalertinib, distinguished by its unique chemical structure, is highly selective for mutant exon 20 compared to wild-type EGFR. Cullinan Therapeutics entered into a collaboration with Taiho Oncology, Inc. in 2022, securing an upfront cash payment of $275 million and additional payments totaling $130 million for future U.S. regulatory approvals in first- and second-line NSCLC treatments. Cullinan retains a 50/50 profit share in the U.S.

Cullinan and Taiho have extensive development plans for zipalertinib, encompassing several pivotal REZILIENT studies. These include ongoing studies in first- and second-line NSCLC with exon20 insertion mutations, as well as trials targeting other patient groups such as those with active brain metastases and uncommon EGFR mutations. Both Module B2 (post-chemotherapy) and Module C (post approved ex20ins treatments) of the REZILIENT1 trial are expected to complete enrollment by the end of 2024.

Cullinan Therapeutics will hold an Investor Event on June 1, 2024, to present an overview of the zipalertinib data and share insights from the 2024 American Society of Clinical Oncology Annual Meeting. Dr. Jeff Jones and Dr. Alexander Spira will provide an overview of the current treatment landscape for EGFR-mutated NSCLC during the event.

Zipalertinib is an orally available small molecule designed to target activating mutations in EGFR, specifically exon 20 insertion mutations, while sparing wild-type EGFR. It is positioned as a next-generation, irreversible EGFR inhibitor for treating a genetically defined subset of NSCLC patients. The drug has received Breakthrough Therapy Designation from the FDA and is being co-developed by Taiho Oncology, Inc., Taiho Pharmaceutical Co., Ltd., and Cullinan Therapeutics, Inc. The rights to zipalertinib in Greater China were previously licensed to Zai Lab Limited in 2020 by Cullinan Pearl Corp., a subsidiary of Cullinan Therapeutics.

Cullinan Therapeutics is committed to developing innovative therapies for cancer and autoimmune diseases. With a strong focus on understanding oncology, immunology, and translational medicine, the company aims to create transformative treatments that address significant unmet medical needs.