Taiho Oncology, Inc. and Cullinan Therapeutics, Inc. (Nasdaq: CGEM) today announced results from Cohort C of the Phase 2 REZILIENT2 trial evaluating zipalertinib monotherapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations or other uncommon EGFR mutations and active central nervous system (CNS) metastases. The data will be presented at the European Society for Medical Oncology (ESMO) Congress 2026, October 23-27, in Madrid, Spain.

Mature results from the first prospective study evaluating intracranial activity of an EGFR tyrosine kinase inhibitor in this patient population demonstrated clinically meaningful intracranial antitumor activity. Among 43 evaluable patients, zipalertinib achieved an intracranial objective response rate of 30% and an intracranial disease control rate of 72%, with a median intracranial duration of response of 9.7 months. Zipalertinib was well tolerated.

“Patients with NSCLC harboring EGFR exon 20 insertion mutations or other uncommon EGFR mutations and active CNS metastases have a significant need for therapies that can effectively address disease in the brain,” said Helena A. Yu, MD, Thoracic Medical Oncologist at Memorial Sloan Kettering Cancer Center and study investigator. “The intracranial responses observed with zipalertinib in REZILIENT2 are encouraging and support continued evaluation of zipalertinib in this difficult-to-treat patient population.”

“The REZILIENT2 results reflect a rigorous examination of the CNS activity of zipalertinib as monotherapy in patients with EGFR ex20ins or uncommon EGFR-mutated NSCLC and active CNS metastases,” said Harold Keer, MD, PhD, Chief Medical Officer, Taiho Oncology. “The findings add to the growing clinical evidence supporting the continued evaluation of zipalertinib in patients with EGFR-mutated NSCLC and brain involvement.”

“The REZILIENT program was designed to explore zipalertinib’s potential in clinically important settings where additional treatment options are needed,” said Jeffrey Jones, MD, MBA, Chief Medical Officer, Cullinan Therapeutics. “Today’s REZILIENT2 update extends that commitment by providing evidence of intracranial activity in patients with active CNS metastases.”

Summary of Results:

Cohort C of REZILIENT2 enrolled patients with NSCLC harboring EGFR ex20ins or other uncommon EGFR mutations and active CNS metastases, including leptomeningeal disease (LMD), irrespective of prior therapy. At the data cutoff, 59 patients were enrolled, with a median follow-up of 9.2 months. Intracranial efficacy was evaluated by Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM), and systemic response was measured by RECIST v1.1.

Among 43 RANO-BM-evaluable patients, including 9 with LMD, 29 (67.4%) had EGFR ex20ins mutations. The median number of prior lines of therapy was two (range 1-6), and 19 patients (44.2%) had received prior EGFR tyrosine kinase inhibitor therapy. In these 43 patients, zipalertinib achieved an intracranial objective response rate (iORR) of 30.2% (95% CI: 17.2, 46.1), an intracranial disease control rate (iDCR) of 72.1% (95% CI: 56.3, 84.7), and a median intracranial duration of response (iDoR) of 9.7 months (95% CI: 3.3, not estimable). Among 24 patients without prior EGFR tyrosine kinase inhibitor exposure, iORR was 37.5%. Systemic efficacy was consistent with intracranial outcomes.

Zipalertinib 100 mg twice daily was well tolerated. Common treatment-related adverse events (TRAEs) included paronychia (32.6%) and diarrhea (25.6%). Grade ≥3 TRAEs occurred in 9 patients (20.9%), including dermatitis acneiform in 4.7% of patients.

Session Information for the ESMO Presentation:

Title: 2621P – Central Nervous System (CNS) Activity of Zipalertinib in Non-Small Cell Lung Cancer (NSCLC) Patients with Uncommon EGFR Mutations (EGFRmt)

Presenting Author: Helena A. Yu, MD, Thoracic Medical Oncologist at Memorial Sloan Kettering Cancer Center and study investigator

Session Date: Monday, October 26, 2026

Session Time: 12:00 p.m.–12:45 p.m. CET

About Zipalertinib

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.

About the REZILIENT2 Trial

REZILIENT2 is a Phase 2b clinical trial (NCT05967689) evaluating zipalertinib in patients with locally advanced or metastatic NSCLC harboring EGFR ex20ins and uncommon single or compound EGFR mutations. Patients were treated with oral zipalertinib 100 mg twice daily. The primary endpoint was ORR and confirmed per investigator-assessed Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 and the secondary endpoints included duration of response (DOR), disease control rate (DCR) and safety.

About EGFR Exon 20 Insertion Mutations

NSCLC is a common form of lung cancer and up to 4% of all cases globally have EGFR ex20ins, which makes them the third most common EGFR mutation subtype.2 In the United States, approximately 16% of patients with NSCLC harbor EGFR mutations,2 with insertions at exon 20 accounting for up to 12% of these mutations.3

About Taiho Oncology, Inc.

The mission of Taiho Oncology, Inc. is to improve the lives of patients with cancer, their families and their caregivers. The company specializes in the development and commercialization of orally administered anti-cancer agents for various tumor types. Taiho Oncology has a robust pipeline of small-molecule clinical candidates targeting solid-tumor and hematological malignancies, with additional candidates in pre-clinical development. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd. which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey and oversees its parent company’s European and Canadian operations, which are located in Baar, Switzerland and Oakville, Ontario, Canada.

For more information, visit https://www.taihooncology.com/, and follow us on LinkedIn and X.

Taiho Oncology and the Taiho Oncology logo are registered trademarks of Taiho Pharmaceutical Co., Ltd.

About Cullinan Therapeutics

Cullinan Therapeutics, Inc. (Nasdaq: CGEM) is a biopharmaceutical company developing potential first- or best-in-class, high-impact therapies for autoimmune diseases and cancer. Cullinan pursues promising therapeutic targets while leveraging core expertise in T cell engagers, which are established in oncology and are now advancing into autoimmune diseases. With a clinical-stage pipeline built on a rigorous scientific approach and purposeful innovation, Cullinan is advancing its mission to deliver new standards of care for patients. Learn more about Cullinan at https://cullinantherapeutics.com/, and follow Cullinan on LinkedIn and X.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding the company’s beliefs and expectations regarding the clinical development of zipalertinib, the safety and efficacy profile of zipalertinib and its potential to address unmet medical need, our plans regarding future data presentations, and other statements that are not historical facts. The words “believe,” “continue,” “could,” “estimate,” “expect,” “intends,” “may,” “plan,” “potential,” “project,” “pursue,” “will,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events and are subject to known and unknown risks and uncertainties that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These risks include, but are not limited to, the following: uncertainty regarding the timing and results of clinical trial data and regulatory submissions; the risk that any NDAs, INDs or other global regulatory submissions we may file with the United States Food and Drug Administration or other global regulatory agencies are not accepted or cleared on our expected timelines, or at all; the success of our clinical trials and preclinical studies; the risks related to our ability to protect and maintain our intellectual property position; the risks related to manufacturing, supply, and distribution of our product candidates; the risk that any one or more of our product candidates, including those that are co-developed, will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical trials will not be predictive of future results in connection with future studies or clinical trials; the effect of changes in global economic conditions, including uncertainties related to international trade policies, tariffs and supply chain dynamics on our business and operations; and the success of any collaboration, partnership, license or similar agreements. These and other important risks and uncertainties discussed in our filings with the Securities and Exchange Commission, including under the caption “Risk Factors” in our most recent Annual Report on Form 10-K and subsequent filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except to the extent required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Moreover, except as required by law, neither the company nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made.

References

  1. Piotrowska Z, Tan DS, Smit EF, et al. Safety, tolerability, and antitumor activity of zipalertinib among patients with non-small-cell lung cancer harboring epidermal growth factor receptor exon 20 insertions. Journal of Clinical Oncology. Available at: https://ascopubs.org/doi/full/10.1200/JCO.23.00152.

  2. Burnett H, Emich H, Carroll C, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. PLOS ONE. 2021;16(3):e0247620. Available at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247620.

  3. Riess JW, Gandara DR, Frampton GM, et al. Diverse EGFR Exon 20 Insertions and Co-Occurring Molecular Alterations Identified by Comprehensive Genomic Profiling of NSCLC. Journal of Thoracic Oncology. 2018 Jul 5;13(10):1560–1568. Available at: https://www.jto.org/article/S1556-0864(18)30770-6/pdf.

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