A Randomized, Placebo-Controlled, Double-Blind, Multi-Center Phase 3 Study of Zipalertinib Plus Adjuvant Chemotherapy Versus Placebo Plus Adjuvant Chemotherapy in Stage IB-IIIA NSCLC Patients With Uncommon EGFR Mutations Following Complete Tumor Resection (REZILIENT4)

The purpose of this study is to compare the efficacy of zipalertinib combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in participants with early stage (stage IB-IIIA) resected non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor mutation (EGFRmt).

Start Date01 Nov 2025

Sponsor / Collaborator

Taiho Oncology, Inc.

CTIS2023-503865-48-00

/ RecruitingPhase 2

An Open-Label, Phase 2b, Global Multicenter Cohort Trial to Assess the Safety and Efficacy of Zipalertinib in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer with Exon 20 Insertion and Uncommon/Single or Compound Epidermal Growth Factor Receptor Mutations - TAS6417-201

Start Date21 Feb 2024

Sponsor / Collaborator

Taiho Oncology, Inc.

NCT05967689

/ RecruitingPhase 2

An Open-Label, Phase 2b, Global Multicenter Cohort Trial to Assess the Safety and Efficacy of Zipalertinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Exon 20 Insertion and Uncommon/Single or Compound Epidermal Growth Factor Receptor Mutations.

The purpose of this study is to evaluate the safety, efficacy and pharmacokinetics (PK) of zipalertinib in participants with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) harboring EGFR ex20ins mutations and other mutations.

Start Date31 Jul 2023

Sponsor / Collaborator

Taiho Oncology, Inc.

100 Clinical Results associated with Zipalertinib

100 Translational Medicine associated with Zipalertinib

100 Patents (Medical) associated with Zipalertinib

Literatures (Medical) associated with Zipalertinib

01 Nov 2025·BIOMEDICAL CHROMATOGRAPHY

Determination of Zipalertinib Using LC‐ESI‐MS/MS and Application to Pharmacokinetic Study in Mice

Article

Author: Das, Arunava ; Dixit, Abhishek

ABSTRACT:

Zipalertinib is a novel, irreversible EGFR inhibitor for the treatment of non‐small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations. A new sensitive, specific and rapid LC‐ESI‐MS/MS method has been developed and validated to quantify zipalertinib in mouse and human dried blood spot (DBS) with filgotinib used as an internal standard (IS) in accordance with regulatory guidelines. Quantification of zipalertinib and IS were achieved by triple quad mass spectrometer operated under the multiple reaction‐monitoring mode (MRM) using positive ion scan mode and parent‐daughter mass to charge ion transition of m/z 397.2 → 326.0 and m/z 426.2 → 291.2, respectively. The linear response function of zipalertinib was determined in the concentration range from 0.741 to 1111 ng/mL (r > 0.990). No matrix effect and carry over were observed. Hematocrit did not influence DBS zipalertinib concentrations. Zipalertinib demonstrated stability under various storage conditions. This method was successfully used to study the in vitro metabolic profiles and in vivo pharmacokinetics of zipalertinib in mice. An excellent correlation was observed between DBS and plasma concentrations, indicating DBS can be used as an alternative for plasma for pharmacokinetic analysis.

19 Feb 2025·Future Oncology

REZILIENT3: randomized phase III study of first-line zipalertinib plus chemotherapy in patients with EGFR exon 20 insertion-mutated NSCLC

Article

Author: Tan, Daniel SW. ; Cheng, Ying ; Heymach, John V. ; Besse, Benjamin ; Wacheck, Volker ; Yu, Helena A. ; Nishio, Makoto ; Wei, Li

There remains a significant unmet need for effective and tolerable treatments for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations in the first-line setting. First and later generation EGFR tyrosine kinase inhibitors (TKIs) have shown efficacy for common EGFR mutations; however, their effectiveness against ex20ins mutations is limited, and platinum-based chemotherapy remains part of the standard of care. Data suggest that combining chemotherapy with EGFR inhibitors offers promise for EGFR ex20ins-mutated NSCLC. REZILIENT3 is an ongoing phase III study evaluating the efficacy and safety of zipalertinib (an orally available, irreversible EGFR-TKI) plus first-line standard-of-care platinum-based chemotherapy with chemotherapy alone in previously untreated patients with nonsquamous NSCLC harboring EGFR ex20ins mutations.Clinical Trial Registration: NCT05973773 (ClinicalTrials.gov).

05 Nov 2024·PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Biochemical analysis of EGFR exon20 insertion variants insASV and insSVD and their inhibitor sensitivity

Article

Author: Eck, Michael J. ; Beyett, Tyler S. ; Rana, Jaimin K. ; Schaeffner, Ilse K. ; Zhao, Hanchen ; Jiang, Jie ; Santana, Jhasmer ; Jänne, Pasi A.

Somatic mutations in the epidermal growth factor receptor (EGFR) are a major cause of non–small cell lung cancer. Among these structurally diverse alterations, exon 20 insertions represent a unique subset that rarely respond to EGFR tyrosine kinase inhibitors (TKIs). Therefore, there is a significant need to develop inhibitors that are active against this class of activating mutations. Here, we conducted biochemical analysis of the two most frequent exon 20 insertion variants, V769_D770insASV (insASV) and D770_N771insSVD (insSVD) to better understand their drug sensitivity and resistance. From kinetic studies, we found that EGFR insASV and insSVD are similarly active, but have lower K m, ATP values compared to the L858R variant, which contributes to their lack of sensitivity to 1st-3rd generation EGFR TKIs. Biochemical, structural, and cellular studies of a diverse panel of EGFR inhibitors revealed that the more recently developed compounds BAY-568, TAS6417, and TAK-788 inhibit EGFR insASV and insSVD in a mutant-selective manner, with BAY-568 being the most potent and selective versus wild-type (WT) EGFR. Cocrystal structures with WT EGFR reveal the binding modes of each of these inhibitors and of poziotinib, a potent but not mutantselective inhibitor, and together they define interactions shared by the mutant-selective agents. Collectively, our results show that these exon20 insertion variants are not inherently inhibitor resistant, rather they differ in their drug sensitivity from WT EGFR. However, they are similar to each other, indicating that a single inhibitor should be effective for several of the diverse exon 20 insertion variants.

News (Medical) associated with Zipalertinib

12 Oct 2025

·www.prnewswire.com

Taiho Oncology and Cullinan Therapeutics Present Data on Zipalertinib in Patients with NSCLC with EGFR mutations and Active Brain Metastases at the ESMO Congress 2025

PRINCETON, N.J. and CAMBRIDGE, Mass., Oct. 12, 2025 /PRNewswire/ -- Taiho Oncology, Inc., and Cullinan Therapeutics, Inc., today announced new data from the central nervous system (CNS) involvement cohort of the REZILIENT2 study of zipalertinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations (ex20ins) or uncommon non-ex20ins EGFR mutations and CNS involvement. Data will be presented at the European Society for Medical Oncology (ESMO) Congress 2025, as a mini oral presentation on October 19 during the "NSCLC metastatic" session from 8:30 to 10 a.m. CEST. Continue Reading Cullinan Therapeutics The mini oral presentation will highlight preliminary efficacy and safety data from the CNS involvement cohort of the ongoing parallel cohort Phase 2b REZILIENT2 trial of zipalertinib.1 Patients with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations represent a significant unmet medical need. An incidence of baseline brain metastases in EGFR ex20ins NSCLC patients ranging from 23% to 39% has been reported.² Patients with lung cancer with CNS involvement have a worse prognosis and require more aggressive therapy, including surgery and radiotherapy. "Treatment options are limited for patients with NSCLC with EGFR mutations and active brain metastases," said Helena A. Yu, MD, Thoracic Medical Oncologist, Memorial Sloan Kettering Cancer. "We are pleased to see that in approximately one-third of patients exposed to zipalertinib, a decrease in CNS lesions was observed. These preliminary results suggest the potential for zipalertinib to treat these patients, warranting future investigation." Authors will report results from the REZILIENT2 study of zipalertinib against active CNS metastases in patients with NSCLC harboring EGFR ex20ins or other uncommon mutations1: Summary of Preliminary Efficacy - by Investigator As of the February 2025 data cutoff, 32 patients were enrolled in the CNS involvement cohort of the ongoing parallel cohort Phase 2b REZILIENT2 trial and received zipalertinib 100 mg orally twice daily. Patients received a median of 2 prior lines of therapy, and of all patients enrolled, 21 patients had ex20ins mutations and 13 patients had other uncommon mutations. As of the data cutoff, zipalertinib demonstrated: In the Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM) criteria evaluable population with measurable CNS disease (n=16, including 3 patients with leptomeningeal disease (LMD), intracranial objective response rate was 31.3% including 1 intracranial complete response. In the same population, the intracranial disease control rate (iDCR) was 68.8% and the median intracranial duration of response (DOR) was 8.1 months. Measured in 29 of the cohort's patients, preliminary systemic objective response rate (ORR) was 27.6% and median DOR was 7.6 months. Intracranial antitumor activity was found to be similar to its overall systemic anticancer activity in this cohort of patients. Summary of Preliminary Safety and Tolerability Administered at 100 mg orally twice daily, zipalertinib was found to be well tolerated, with no new safety signals observed. Treatment-related adverse events of grade 3 or higher occurred in 8 patients (25%) and included anemia (n=3) and interstitial lung disease (n=2). There was one death due to interstitial lung disease. About REZILIENT2 REZILIENT2 is a Phase 2b clinical trial (NCT05967689), evaluating the safety and efficacy of zipalertinib in patients with locally advanced or metastatic NSCLC harboring ex20ins mutations or other uncommon/single or compound EGFR mutations. Patients are enrolled into one of four cohorts: Cohort A ("prior ex20ins treatment"), Cohort B ("first-line"), Cohort C ("active brain metastases"), and Cohort D ("other uncommon EGFR mutations"). Cohort C includes patients harboring EFGR ex20ins or other uncommon/single or compound EGFR mutations and CNS involvement. In this cohort, patients may or may not have had prior treatment for advanced disease. Patients are treated with oral zipalertinib 100 mg twice daily. The primary endpoint is ORR and confirmed per investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and the secondary endpoints include DOR, DCR, PFS, OS, intracranial efficacy by RANO-BM criteria, PK and safety. 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 ex20ins 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 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 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 , 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 dedicated to creating new standards of care for patients. Cullinan has strategically built a diversified portfolio of clinical-stage assets that inhibit key drivers of disease or harness the immune system to eliminate diseased cells in both autoimmune diseases and cancer. Cullinan's portfolio encompasses a wide range of modalities, each with the potential to be best and/or first in class. Anchored in a deep understanding of oncology, immunology, and translational medicine, we create differentiated ideas, identify the most appropriate targets, and select the optimal modality to develop transformative therapeutics across a wide variety of autoimmune and cancer indications. We push conventional boundaries from candidate selection to differentiated therapeutic, applying rigorous go/no go criteria at each stage of development to fast-track only the most promising molecules to the clinic and, ultimately, commercialization. With deep scientific expertise, our teams exercise creativity and urgency to deliver on our promise to bring new therapeutic solutions to patients. Learn more about Cullinan at , and follow us 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 our plans regarding future data presentations, the clinical development and regulatory filing plan and timeline of zipalertinib, the safety and efficacy profile of zipalertinib and its potential to address unmet medical need, 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 regulatory submissions; the risk that any NDA or other regulatory submissions we may file with the United States Food and Drug Administration or other global regulatory agencies are not 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 studies will not be predictive of future results in connection with future studies; 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. Contacts Taiho Oncology Leigh Labrie (609) 664-9878 [email protected] Cullinan Therapeutics Investors Nick Smith +1 401.241.3516 [email protected] Media Rose Weldon +1 215.801.7644 [email protected] References K. Ohashi et al. Activity of Zipalertinib Against Active Central Nervous System (CNS) Metastases in Patients With Non-Small Cell Lung Cancer (NSCLC) Harboring EGFR Exon 20 Insertion (Ex20ins)/Other Uncommon Mutations. Remon J. et al. EGFR exon 20 insertions in advanced non-small cell lung cancer: A new history begins. Cancer Treatment Review. Volume 90, November 2020, 102105. SOURCE Taiho Oncology WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2Clinical ResultBreakthrough TherapyDrug Approval

12 Oct 2025

·investors.cullinantherapeutics.com

Taiho Oncology and Cullinan Therapeutics Present Data on Zipalertinib in Patients with NSCLC with EGFR Mutations and Active Brain Metastases at the ESMO Congress 2025

Princeton, N.J., Cambridge, Mass., Oct. 12, 2025 — Taiho Oncology, Inc., and Cullinan Therapeutics, Inc., today announced new data from the central nervous system (CNS) involvement cohort of the REZILIENT2 study of zipalertinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations (ex20ins) or uncommon non-ex20ins EGFR mutations and CNS involvement. Data will be presented at the European Society for Medical Oncology (ESMO) Congress 2025, as a mini oral presentation on October 19 during the “NSCLC metastatic” session from 8:30 to 10 a.m. CEST. The mini oral presentation will highlight preliminary efficacy and safety data from the CNS involvement cohort of the ongoing parallel cohort Phase 2b REZILIENT2 trial of zipalertinib 1. Patients with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations represent a significant unmet medical need. An incidence of baseline brain metastases in EGFR ex20ins NSCLC patients ranging from 23% to 39% has been reported.2 Patients with lung cancer with CNS involvement have a worse prognosis and require more aggressive therapy, including surgery and radiotherapy. “Treatment options are limited for patients with NSCLC with EGFR mutations and active brain metastases,” said Helena A. Yu, MD, Thoracic Medical Oncologist, Memorial Sloan Kettering Cancer.“We are pleased to see that in approximately one-third of patients exposed to zipalertinib, a decrease in CNS lesions was observed. These preliminary results suggest the potential for zipalertinib to treat these patients, warranting future investigation.” Authors will report results from the REZILIENT2 study of zipalertinib against active CNS metastases in patients with NSCLC harboring EGFR ex20ins or other uncommon mutations1: Summary of Preliminary Efficacy - by Investigator As of the February 2025 data cutoff, 32 patients were enrolled in the CNS involvement cohort of the ongoing parallel cohort Phase 2b REZILIENT2 trial and received zipalertinib 100 mg orally twice daily. Patients received a median of 2 prior lines of therapy, and of all patients enrolled, 21 patients had ex20ins mutations and 13 patients had other uncommon mutations. As of the data cutoff, zipalertinib demonstrated: In the Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM) criteria evaluable population with measurable CNS disease (n=16, including 3 patients with leptomeningeal disease (LMD), intracranial objective response rate was 31.3% including 1 intracranial complete response. In the same population, the intracranial disease control rate (iDCR) was 68.8% and the median intracranial duration of response (DOR) was 8.1 months. Measured in 29 of the cohort’s patients, preliminary systemic objective response rate (ORR) was 27.6% and median DOR was 7.6 months. Intracranial antitumor activity was found to be similar to its overall systemic anticancer activity in this cohort of patients. Summary of Preliminary Safety and Tolerability Administered at 100 mg orally twice daily, zipalertinib was found to be well tolerated, with no new safety signals observed. Treatment-related adverse events of grade 3 or higher occurred in 8 patients (25%) and included anemia (n=3) and interstitial lung disease (n=2). There was one death due to interstitial lung disease. About REZILIENT2 REZILIENT2 is a Phase 2b clinical trial (NCT05967689), evaluating the safety and efficacy of zipalertinib in patients with locally advanced or metastatic NSCLC harboring ex20ins mutations or other uncommon/single or compound EGFR mutations. Patients are enrolled into one of four cohorts: Cohort A (“prior ex20ins treatment”), Cohort B (“first-line”), Cohort C (“active brain metastases”), and Cohort D (“other uncommon EGFR mutations”). Cohort C includes patients harboring EFGR ex20ins or other uncommon/single or compound EGFR mutations and CNS involvement. In this cohort, patients may or may not have had prior treatment for advanced disease. Patients are treated with oral zipalertinib 100 mg twice daily. The primary endpoint is ORR and confirmed per investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and the secondary endpoints include DOR, DCR, PFS, OS, intracranial efficacy by RANO-BM criteria, PK and safety. 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 ex20ins 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 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 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 dedicated to creating new standards of care for patients. Cullinan has strategically built a diversified portfolio of clinical-stage assets that inhibit key drivers of disease or harness the immune system to eliminate diseased cells in both autoimmune diseases and cancer. Cullinan’s portfolio encompasses a wide range of modalities, each with the potential to be best and/or first in class. Anchored in a deep understanding of oncology, immunology, and translational medicine, we create differentiated ideas, identify the most appropriate targets, and select the optimal modality to develop transformative therapeutics across a wide variety of autoimmune and cancer indications. We push conventional boundaries from candidate selection to differentiated therapeutic, applying rigorous go/no go criteria at each stage of development to fast-track only the most promising molecules to the clinic and, ultimately, commercialization. With deep scientific expertise, our teams exercise creativity and urgency to deliver on our promise to bring new therapeutic solutions to patients. Learn more about Cullinan at https://cullinantherapeutics.com/, and follow us 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 our plans regarding future data presentations, the clinical development and regulatory filing plan and timeline of zipalertinib, the safety and efficacy profile of zipalertinib and its potential to address unmet medical need, 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 regulatory submissions; the risk that any NDA or other regulatory submissions we may file with the United States Food and Drug Administration or other global regulatory agencies are not 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 studies will not be predictive of future results in connection with future studies; 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. Contacts Taiho Oncology Leigh Labrie (609) 664-9878 llabrie@taihooncology.com Cullinan Therapeutics Investors Nick Smith +1 401.241.3516 nsmith@cullinantx.com Media Rose Weldon +1 215.801.7644 rweldon@cullinantx.com References

Phase 2Clinical ResultBreakthrough TherapyDrug Approval

10 Sep 2025

·www.biospace.com

Cullinan, Taiho’s NSCLC Hopeful Shows ‘Strong Activity,’ Clearing Road to FDA

iStock, Deagreez Cullinan Therapeutics and Taiho Oncology’s zipalertinib elicited promising response rates in two mid-stage studies of non-small cell lung cancer patients with typical and uncommon EGFR mutations. Cullinan Therapeutics and Taiho Oncology touted promising efficacy and safety data for their investigational tyrosine kinase inhibitor zipalertinib in certain types of non-small cell lung cancer, showing data in a pair of presentations Tuesday. One Phase I/II study, dubbed REZILIENT1, involved 84 patients with NSCLC who harbored exon 20 insertion mutations in the EGFR gene. Study participants had undergone a median of three previous lines of therapy, including with Johnson & Johnson’s bispecific antibody Rybrevant. Results, presented at the 2025 World Conference on Lung Cancer, revealed a 27.4% objective response rate (ORR) and 84.5% disease control rate (DCR). Median duration of response was 8.5 months. Zipalertinib appeared to be more effective as a second-line option in patients who had only been previously exposed to Rybrevant. ORR was 31.5% in that subgroup and DCR Increased to 87%. Analysts at William Blair expressed optimism about zipalertinib’s prospects. “We believe zipalertinib continues to show strong efficacy in previously treated (with both chemotherapy and Rybrevant) patients, which along with its favorable tolerability pro bode well for potential uptake in the second-line setting,” the analysts wrote in a note to investors Tuesday afternoon. Meanwhile, the second study, a Phase IIb trial called REZILIENT2, focused on patients with “uncommon” NSCLC mutations—non-exon 20 insertions in the EGFR gene—according to Tuesday’s release. Participants had likewise undergone prior lines of treatment, though Taiho and Cullinan did not specify that this had to be with Rybrevant. Zipalertinib treatment elicited a 30% ORR and a 70% DCR in this group. Median duration of response was 7.75 months. Taken together, according to the William Blair analysts, zipalertinib’s efficacy data on Tuesday point to the drug’s “strong activity” in these two NSCLC patient populations. Taiho and Cullinan are building up to a regulatory submission by the end of the year for NSCLC with EGFR exon 20 insertions, according to the analyst firm. REZILIENT2, in particular, “could support a meaningful expansion opportunity” for zipalertinib into patients harboring uncommon non-exon 20 mutations, according to William Blair. There are no submission plans for this specific population yet, as per the analysts’ note, but Taiho and Cullinan are scheduled to present findings from the study at the upcoming ESMO Congress next month. Several other biopharma players have released major lung cancer readouts in recent days. Merck and Daiichi Sankyo on Sunday announced that their antibody-drug conjugate ifinatamab deruxtecan yielded a 48.2% confirmed objective response rate in patients with extensive-stage small cell lung cancer. The partners reported three complete responses. Also on Sunday, Summit Therapeutics released data from the Phase III HARMONi study of its closely watched bispecific antibody ivonescimab in NSCLC. The biotech had already announced in May that HARMONi fell short of its overall survival bar, but Sunday’s readout additionally showed that survival outcomes appeared to be better in Asian patients than those in Western countries.

Clinical ResultPhase 2Phase 3ADCASCO

100 Deals associated with Zipalertinib

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-small cell lung cancer stage IIIA	Phase 3	United States	Taiho Oncology, Inc.	01 Nov 2025
Non-small cell lung cancer stage IIIA	Phase 3	Japan	Taiho Oncology, Inc.	01 Nov 2025
Non-small cell lung cancer stage IIIA	Phase 3	Argentina	Taiho Oncology, Inc.	01 Nov 2025
Non-small cell lung cancer stage IIIA	Phase 3	Australia	Taiho Oncology, Inc.	01 Nov 2025
Non-small cell lung cancer stage IIIA	Phase 3	Belgium	Taiho Oncology, Inc.	01 Nov 2025
Non-small cell lung cancer stage IIIA	Phase 3	Brazil	Taiho Oncology, Inc.	01 Nov 2025
Non-small cell lung cancer stage IIIA	Phase 3	Canada	Taiho Oncology, Inc.	01 Nov 2025
Non-small cell lung cancer stage IIIA	Phase 3	France	Taiho Oncology, Inc.	01 Nov 2025
Non-small cell lung cancer stage IIIA	Phase 3	Germany	Taiho Oncology, Inc.	01 Nov 2025
Non-small cell lung cancer stage IIIA	Phase 3	Greece	Taiho Oncology, Inc.	01 Nov 2025

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05967689 (REZILIENT2, ESMO2025)	Phase 2	EGFR ex20ins mutation in non-small cell lung cancer EGFR S768I \| EGFR Exon 20 Insertion \| EGFR L861Q ... View more	32	Zipalertinib 100 mg	vjrbyvqzyu \| hapheqfdwd(strssrqevr) = bqvtldhzme ygqmetbghe (beychqweoj, 41.3 - 89.0) View more	Positive	17 Oct 2025
NCT05967689 (REZILIENT2，TAS6417-201, WCLC2025)	Phase 2	Advanced Lung Non-Small Cell Carcinoma Second line \| First line EGFR S768I/L861Q/G719X Mutation	80	Zipalertinib 100 mg orally twice daily	pmgtxsmcfn(fgovdfmiug) = jonfuvnqyw fstdtjficf (hiyubnemtp, 16.6 - 46.5) View more	Positive	09 Sep 2025
NCT05967689 (REZILIENT2，TAS6417-201, WCLC2025)	Phase 2		80	Zipalertinib 100 mg orally twice daily (treatment-naïve patients)	pmgtxsmcfn(fgovdfmiug) = wtlwtohhdy fstdtjficf (hiyubnemtp, 24.5 - 91.5)	Positive	09 Sep 2025
NCT04036682 (REZILIENT1, Pubmed \| J Clin Oncol)	Phase 1/2	EGFR positive non-small cell lung cancer EGFR exon 20 insertion	244	Zipalertinib 100 mg twice daily	cjabiotzsz(lxogkmdvnm) = zrpjxdvsxx mjfwytcjnf (nmdudrbyco, 28.2 - 42.8) View more	Positive	01 Jun 2025
NCT04036682 (REZILIENT1, Pubmed \| J Clin Oncol)	Phase 1/2		244	Platinum-based chemotherapy without ex20ins-targeted therapy	cjabiotzsz(lxogkmdvnm) = rpunhieiwc mjfwytcjnf (nmdudrbyco ) View more	Positive	01 Jun 2025
NCT04036682 (REZILIENT1, ASCO2025) Manual	Phase 2	EGFR ex20ins mutation in non-small cell lung cancer EGFR Exon 20 Insertion	176	Zipalertinib 100mgZipalertinib 100mg+platinum-based chemotherapy	nwegfeuhnj(sbbagqyjpi) = vllijujtiv vqzkifygoc (gdgaqsausm ) View more	Positive	30 May 2025
NCT04036682 (REZILIENT1, ASCO2025) Manual	Phase 2		176	zipalertinib 100mgzipalertinib 100mg+platinum-based chemotherapy +amivantamab	nwegfeuhnj(sbbagqyjpi) = prefmejcgw vqzkifygoc (gdgaqsausm ) View more	Positive	30 May 2025
NCT04036682 (REZILIENT1, PRNewswire) Manual	Phase 2	EGFR ex20ins mutation in non-small cell lung cancer Second line EGFR Exon 20 Insertion	-	Zipalertinib	oljhuhuwry(pngvdpvoth) = met its primary endpoint of overall response rate hcavwxdlbg (krgdpymymf ) Met	Positive	28 Jan 2025
NCT04036682 (REZILIENT1, WCLC2025 \| Pubmed \| NEWS 1 \| NEWS 2 \| NEWS 3 \| NEWS 4 \| ASCO2025)	Phase 2	Advanced Lung Non-Small Cell Carcinoma Second line EGFR ex20ins mutation	244	Zipalertinib 100 mg BID (prior plt-chemo with or without prior ami)	mdmsrshldo(zczszntpsi) = xlidvwpmgv vnfgqkzuid (dlgotmgkqg, 28.2 - 42.8) View more	Positive	28 Jan 2025
	Phase 2		244	Zipalertinib 100 mg BID (prior plt-chemo)	mdmsrshldo(zczszntpsi) = rfdfxxalyx vnfgqkzuid (dlgotmgkqg, 31.3 - 49.1) View more	Positive	28 Jan 2025
NCT05973773 (REZILIENT3, ESMO_ASIA2024) Manual	Phase 3	EGFR ex20ins mutation in non-small cell lung cancer First line EGFR exon 20 insertion	6	Zipalertinib 100 mg PO BID + Chemotherapy	odbeentfnb(qnbxdaqven) = gcxohaohss pkmzisjvjf (gxmxvrtfnr )	Positive	07 Dec 2024
NCT04036682 (REZILIENT1, ESMO2024) Manual	Phase 2	EGFR ex20ins mutation in non-small cell lung cancer Second line EGFR Exon 20 Insertion	45	Zipalertinib 100 mg oral twice daily	ujtisofmzo(agaynlqkqe) = cxnhqcvogv jbsfnrfinm (iqeybnafmq ) View more	Positive	14 Sep 2024
NCT04036682 (REZILIENT1, Biospace) Manual	Phase 2	EGFR ex20ins mutation in non-small cell lung cancer	18	Zipalertinib	sfbxodfsyu(scmikwdzfs) = pluqaqmgip nakasomkld (gunnsrvsuj ) View more	Positive	01 Jun 2024
NCT04036682 (Pubmed)	Phase 1/2	EGFR-mutated non-small Cell Lung Cancer	73	Zipalertinib	ygifrxcbcf(lupxgvinca) = huwoiarxnd fqlimprleb (crhwibnojv ) View more	-	29 Jun 2023

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