This phase II trial tests how well zipalertinib with carboplatin and pemetrexed works in treating stage II-IIIB non small cell lung cancer. that can be removed by surgery (resectable). Zipalertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make DNA and may kill tumor cells. Giving zipalertinib with carboplatin and pemetrexed may kill more tumor cells in patients with resectable, stage II-IIIB non-small cell lung cancer.

Start Date01 Jun 2027

Sponsor / Collaborator

Jonsson Comprehensive Cancer Center

[+1]

NCT07128199

/ RecruitingPhase 3

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 Date22 Dec 2025

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.

01 Jun 2025·LUNG CANCER

Novel strategies for rare oncogenic drivers in non-small-cell lung cancer: An update from the 2024 Annual ESMO meeting

Review

Author: van der Wel, J W T ; de Langen, A J

Across the landscape of oncogene-addicted non-small-cell lung cancer (NSCLC), various tyrosine kinase inhibitors (TKIs) have been introduced in the last twenty years. During the 2024 Annual ESMO meeting new therapeutic options were presented for EGFR exon 20 insertion mutation, ALK fusion and ROS1 fusion positive advanced stage NSCLC. For EGFR exon 20 insertion mutation positive NSCLC, results from REZILIENT-1, a single arm phase II study with zipalertinib, were presented, showing an objective response rate (ORR) of 50% in patients that were pretreated with amivantamab, and 25% in patients pretreated with amivantamab and an EGFR exon 20 insertion-directed TKI. The vast majority of these patients also received platinum-doublet chemotherapy. For ALK, results from ALKOVE-1, a single arm phase I/II study with NVL-655, a next generation ALK TKI, were presented. The ORR was 35 % in patients pretreated with ≥ 2 ALK TKIs including lorlatinib and 57 % in patients pretreated with ≥ 1 ALK TKI, excluding lorlatinib. The median number of prior anticancer therapies was 3. Intracranial responses were seen in lorlatinib naïve- and lorlatinib pretreated patients and toxicity was manageable. In addition, results of the first-line randomized phase III INSPIRE study were presented, in which iruplinalkib, an ALK and ROS1 selective TKI, is being evaluated versus crizotinib. Iruplinalkib showed a superior median PFS (36.8 versus 14.55 months for crizotinib), but no difference in 36-month overall survival (OS) rate. Finally, results from ARROS-1, a single arm phase I/II study with zidesamtinib, a ROS1 selective and TRK-sparing TKI, were presented. An ORR of 73% was obtained in patients that were pretreated with crizotinib and an ORR of 38% in patients pretreated with repotrectinib. In this review, we will discuss the relevant study results presented at ESMO 2024 for these three genomic drivers and hypothesize on their respective place in the sequence of treatment options.

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).

News (Medical) associated with Zipalertinib

08 Jan 2026

·investors.cullinantherapeutics.com

Cullinan Therapeutics Provides Corporate Update and Highlights Anticipated 2026 Milestones

Data readouts planned for CLN-978 across all three autoimmune indications in 2026, including single dose and repeat dosing data Company to complete monotherapy expansion cohorts to determine recommended Phase 2 dose for CLN-049 pivotal registrational study and initiate combination study in frontline AML in Q4 2026 Zipalertinib rolling NDA submission expected to be complete in Q1 2026 and full enrollment of REZILIENT3 frontline study expected in H1 2026 Preliminary cash and investments of $439.0 million as of December 31, 2025; Runway into 2029 CAMBRIDGE, Mass., Jan. 08, 2026 (GLOBE NEWSWIRE) -- Cullinan Therapeutics, Inc. (Nasdaq: CGEM; “Cullinan”), a clinical-stage biopharmaceutical company accelerating potential first- or best-in-class, high-impact therapies in autoimmune diseases and cancer, today provided a corporate update and shared anticipated business highlights for 2026. “We have built strong momentum with CLN-978 and are pleased to share that we have completed multiple dose cohorts in our OUTRACE RA and OUTRACE SLE studies, and we have initiated dosing in our Sjögren’s disease study. This significant progress positions us to deliver the first company sponsored data with a CD19 T cell engager in autoimmune diseases. Throughout 2026, we will deliver data across all three indications, including important repeat dosing data in rheumatoid arthritis,” said Nadim Ahmed, President and CEO of Cullinan Therapeutics. “Our CLN-049 program continues to advance following the presentation of compelling efficacy and favorable safety data at ASH 2025, which we believe enables an accelerated approval pathway. We plan to complete dose expansion in relapsed/refractory AML and TP53m AML to rapidly determine a recommended Phase 2 dose, while also initiating a frontline combination study this year. Additionally, 2026 marks a pivotal milestone for zipalertinib, as Taiho completes the rolling NDA submission in the beginning of the year, and completes enrollment in the frontline study REZILIENT3 in the first half of 2026. In summary, we are focused on generating multiple catalysts for our two high-priority T cell engager programs, CLN-978 and CLN-049, positioning us for a transformative year ahead.” Portfolio Highlights and Anticipated 2026 Milestones Immunology CLN-978 (CD19xCD3 bispecific T cell engager): Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren’s disease (SjD) OUTRACE RA Dose escalation is ongoing, and patients are currently being enrolled to the 30-microgram dose cohort. The 10- and 20-microgram dose cohorts are complete with no dose-limiting toxicities observed. In Q2 2026, the Company plans to share initial data from the single target dose escalation portion of the study with a focus on safety and B cell depletion in peripheral blood and tissue, additional biomarker data, and preliminary clinical activity data. In Q3 2026, the Company plans to share initial repeat dosing data, including B cell depletion in peripheral blood and tissue, additional biomarker data, and preliminary clinical activity data. OUTRACE SLE Dose escalation is ongoing, and patients are currently being enrolled in the 30-microgram dose cohort. The 10- and 20-microgram dose cohorts are complete with no dose-limiting toxicities observed. In Q2 2026, the Company plans to share initial data from Part A (single target dose escalation) with a focus on safety and B cell depletion in peripheral blood, additional biomarker data, and preliminary clinical activity data. OUTRACE SjD The Company has initiated patient dosing, and enrollment is ongoing in the 10-microgram dose cohort. In Q4 2026, the Company plans to share initial data from Part A (single target dose escalation) with a focus on safety and B cell depletion in peripheral blood and tissue, additional biomarker data, and preliminary clinical activity data. Velinotamig (BCMAxCD3 bispecific T cell engager): Autoimmune diseases In December 2025, Genrix Bio initiated a Phase 1 study in China in patients with autoimmune diseases, and initial clinical data from the study will be shared in Q4 2026. Cullinan intends to use the data generated to accelerate global clinical development of the program. Following the completion of the Genrix Bio Phase 1 study, Cullinan will conduct all further development of velinotamig in autoimmune diseases. Dose escalation is ongoing, and patients are currently being enrolled to the 30-microgram dose cohort. The 10- and 20-microgram dose cohorts are complete with no dose-limiting toxicities observed. In Q2 2026, the Company plans to share initial data from the single target dose escalation portion of the study with a focus on safety and B cell depletion in peripheral blood and tissue, additional biomarker data, and preliminary clinical activity data. In Q3 2026, the Company plans to share initial repeat dosing data, including B cell depletion in peripheral blood and tissue, additional biomarker data, and preliminary clinical activity data. Dose escalation is ongoing, and patients are currently being enrolled in the 30-microgram dose cohort. The 10- and 20-microgram dose cohorts are complete with no dose-limiting toxicities observed. In Q2 2026, the Company plans to share initial data from Part A (single target dose escalation) with a focus on safety and B cell depletion in peripheral blood, additional biomarker data, and preliminary clinical activity data. The Company has initiated patient dosing, and enrollment is ongoing in the 10-microgram dose cohort. In Q4 2026, the Company plans to share initial data from Part A (single target dose escalation) with a focus on safety and B cell depletion in peripheral blood and tissue, additional biomarker data, and preliminary clinical activity data. In December 2025, Genrix Bio initiated a Phase 1 study in China in patients with autoimmune diseases, and initial clinical data from the study will be shared in Q4 2026. Cullinan intends to use the data generated to accelerate global clinical development of the program. Following the completion of the Genrix Bio Phase 1 study, Cullinan will conduct all further development of velinotamig in autoimmune diseases. Oncology CLN-049 (FLT3xCD3 bispecific T cell engager): Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) In December 2025, CLN-049 received Fast Track designation for the treatment of relapsed/refractory AML from the U.S. FDA and, in an oral presentation at the 2025 ASH Annual Meeting, the Company shared compelling clinical data in a heavily pretreated all-comer population of patients with relapsed/refractory AML. The Company plans to share an update from the dose escalation portion of the study in H2 2026. In Q2 2026, the Company expects to initiate monotherapy dose expansion cohorts in patients with relapsed/refractory AML and TP53m AML. In Q4 2026, the Company expects to complete enrollment for dose expansion to determine the recommended Phase 2 dose (RP2D) for an expected single arm pivotal registrational trial. In Q4 2026, the Company plans to initiate a Phase 1/2 combination study in frontline AML. Enrollment also continues in a parallel Phase 1 study in patients with AML and measurable residual disease (MRD) immediately following induction therapy. Zipalertinib (EGFR ex20ins inhibitor), collaboration with Taiho Oncology: EGFR ex20ins NSCLC In November 2025, Taiho initiated a rolling submission of an NDA seeking accelerated approval of zipalertinib for the treatment of patients with relapsed EGFR ex20ins NSCLC. Taiho expects completion of the NDA submission in Q1 2026. Taiho expects to complete enrollment of the pivotal study REZILIENT3 in 1L EGFR ex20ins NSCLC in H1 2026. Cullinan is eligible to receive up to $130 million in payments for U.S. regulatory milestones and a 50/50 profit share in the U.S. In December 2025, CLN-049 received Fast Track designation for the treatment of relapsed/refractory AML from the U.S. FDA and, in an oral presentation at the 2025 ASH Annual Meeting, the Company shared compelling clinical data in a heavily pretreated all-comer population of patients with relapsed/refractory AML. The Company plans to share an update from the dose escalation portion of the study in H2 2026. In Q2 2026, the Company expects to initiate monotherapy dose expansion cohorts in patients with relapsed/refractory AML and TP53m AML. In Q4 2026, the Company expects to complete enrollment for dose expansion to determine the recommended Phase 2 dose (RP2D) for an expected single arm pivotal registrational trial. In Q4 2026, the Company plans to initiate a Phase 1/2 combination study in frontline AML. Enrollment also continues in a parallel Phase 1 study in patients with AML and measurable residual disease (MRD) immediately following induction therapy. In November 2025, Taiho initiated a rolling submission of an NDA seeking accelerated approval of zipalertinib for the treatment of patients with relapsed EGFR ex20ins NSCLC. Taiho expects completion of the NDA submission in Q1 2026. Taiho expects to complete enrollment of the pivotal study REZILIENT3 in 1L EGFR ex20ins NSCLC in H1 2026. Cullinan is eligible to receive up to $130 million in payments for U.S. regulatory milestones and a 50/50 profit share in the U.S. Cash Position and Cash RunwayUnaudited preliminary cash, cash equivalents, short- and long-term investments, and interest receivable were $439.0 million as of December 31, 2025. Consistent with prior guidance, Cullinan expects its cash resources to provide runway into 2029 under its current operating plan. The Company expects to report its fourth quarter and full-year 2025 financial results in late February 2026 which will contain additional information required for a more complete understanding of the Company’s financial position and results of operations as of and for the year ended December 31, 2025. 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 StatementsThis 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 preclinical and clinical developments plans and timelines for our product candidates, the clinical and therapeutic potential of our product candidates, the strategy of our product candidates, our research and development activities, our preliminary estimates of cash, cash equivalents, short- and long-term investments, and interest receivable as of December 31, 2025, our cash runway, 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: the preliminary cash position reported herein reflects information available to us only at this time and may differ from our actual cash position as of December 31, 2025, including in connection with the completion of our financial statement closing procedures; uncertainty regarding the timing and results of regulatory submissions; the risk that any INDs, NDAs or other global regulatory submissions we may file with the United States Food and Drug Administration or other global regulatory agencies are not cleared or approved 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; 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. Contacts: InvestorsNick Smith+1 401.241.3516nsmith@cullinantx.com Media  Rose Weldon +1 215.801.7644 rweldon@cullinantx.com

Phase 1Fast Track

21 Nov 2025

·www.taiho.co.jp

Taiho Oncology, Taiho Pharmaceutical and Cullinan Therapeutics Initiate Rolling Submission of NDA to U.S. Food and Drug Administration for Zipalertinib for Treatment of Locally Advanced or Metastatic NSCLC with EGFR Exon 20 Insertion Mutations

Taiho Oncology, Inc., Taiho Pharmaceutical Co., Ltd., and Cullinan Therapeutics, Inc. (Nasdaq: CGEM) announced the companies have initiated the rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval of zipalertinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations who have previously received platinum-based systemic chemotherapy. Zipalertinib previously received Breakthrough Therapy Designation in 2021, which with FDA agreement, allows submission of portions of the application as they are completed. The companies anticipate completion of the NDA submission in the first quarter of 2026 with an associated request for priority review. The NDA submission is based on the primary efficacy data from the REZILIENT1 trial, a Phase 1/2 clinical trial of zipalertinib (development code: CLN-081/TAS6417) monotherapy in patients with NSCLC harboring EGFR ex20ins mutations who have received prior therapy. Positive results from the REZILIENT1 trial were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and were simultaneously published in the Journal of Clinical Oncology. REZILIENT1 (Researching Zipalertinib In EGFR Non-Small Cell Lung Cancer Tumors) is a Phase 1/2 clinical trial (NCT04036682) to evaluate efficacy and safety of zipalertinib in adult patients with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations who have received prior therapy. Patients were treated with oral zipalertinib 100 mg twice daily. The primary endpoints were objective response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review (ICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Adverse events were characterized and graded according to the NCI-Common Terminology Criteria for Adverse Events (CTCAE v5.0). 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, 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. NSCLC is a common form of lung cancer and up to 4% of all cases globally have EGFR exon 20 insertions, which makes them the third most common EGFR mutation subtype.1 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.1 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. Taiho Pharmaceutical, a subsidiary of Otsuka Holdings Co., Ltd. (https://www.otsuka.com/en/), is an R&D-driven specialty pharma focusing on the fields of oncology and immune-related diseases. Its corporate philosophy takes the form of a pledge: “We strive to improve human health and contribute to a society enriched by smiles.” In the field of oncology, in particular, Taiho Pharmaceutical is known as a leading company in Japan for developing innovative medicines for the treatment of cancer, a reputation that is rapidly expanding through their extensive global R&D efforts. In areas other than oncology, as well, the company creates and markets quality products that effectively treat medical conditions and can help improve people’s quality of life. Always putting customers first, Taiho Pharmaceutical also aims to offer consumer healthcare products that support people’s efforts to lead fulfilling and rewarding lives. For more information about Taiho Pharmaceutical, please visit https://www.taiho.co.jp/en. 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.

Priority ReviewBreakthrough TherapyNDAASCOClinical Study

20 Nov 2025

·www.taihooncology.com

Taiho Oncology, Taiho Pharmaceutical and Cullinan Therapeutics Initiate Rolling Submission of New Drug Application to U.S. Food and Drug Administration for Zipalertinib for Treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer with E

PRINCETON, New Jersey, TOKYO, Japan, CAMBRIDGE, Mass., Nov. 20, 2025 — Taiho Oncology, Inc., Taiho Pharmaceutical Co., Ltd., and Cullinan Therapeutics, Inc. (Nasdaq: CGEM) today announced the companies have initiated the rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval of zipalertinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations who have previously received platinum-based systemic chemotherapy. Zipalertinib previously received Breakthrough Therapy Designation in 2021, which with FDA agreement, allows submission of portions of the application as they are completed. The companies anticipate completion of the NDA submission in the first quarter of 2026 with an associated request for priority review. The NDA submission is based on the primary efficacy data from the REZILIENT1 trial, a Phase 1/2 clinical trial of zipalertinib (development code: CLN-081/TAS6417) monotherapy in patients with NSCLC harboring EGFR ex20ins mutations who have received prior therapy. Positive results from the REZILIENT1 trial were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and were simultaneously published in the Journal of Clinical Oncology. About REZILIENT1 REZILIENT1 (Researching Zipalertinib In EGFR Non-Small Cell Lung Cancer Tumors) is a Phase 1/2 clinical trial (NCT04036682) to evaluate efficacy and safety of zipalertinib in adult patients with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations who have received prior therapy. Patients were treated with oral zipalertinib 100 mg twice daily. The primary endpoints were objective response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review (ICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Adverse events were characterized and graded according to the NCI-Common Terminology Criteria for Adverse Events (CTCAE v5.0). 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, 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 EGFR Exon 20 Insertion Mutations NSCLC is a common form of lung cancer and up to 4% of all cases globally have EGFR exon 20 insertions, which makes them the third most common EGFR mutation subtype.1 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.1 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 Taiho Pharmaceutical Co., Ltd. (Japan) Taiho Pharmaceutical, a subsidiary of Otsuka Holdings Co., Ltd. (https://www.otsuka.com/en/), is an R&D-driven specialty pharma focusing on the fields of oncology and immune-related diseases. Its corporate philosophy takes the form of a pledge: “We strive to improve human health and contribute to a society enriched by smiles.” In the field of oncology, in particular, Taiho Pharmaceutical is known as a leading company in Japan for developing innovative medicines for the treatment of cancer, a reputation that is rapidly expanding through their extensive global R&D efforts. In areas other than oncology, as well, the company creates and markets quality products that effectively treat medical conditions and can help improve people’s quality of life. Always putting customers first, Taiho Pharmaceutical also aims to offer consumer healthcare products that support people’s efforts to lead fulfilling and rewarding lives. For more information about Taiho Pharmaceutical, please visit https://www.taiho.co.jp/en. 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 initiation and expected timing for completion of its rolling NDA submission to the FDA, the clinical development 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 NDAs, INDs or other 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 studies will not be predictive of future results in connection with future studies; 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. Contacts Taiho Oncology Leigh Labrie +1 609.664.9878 llabrie@taihooncology.com Taiho Pharmaceutical Co., Ltd. Junko Onishi +81-80-1009-7683 junn-onishi@taiho.co.jp Cullinan Therapeutics Investors Nick Smith +1 401.241.3516 nsmith@cullinantx.com Media Rose Weldon +1 215.801.7644 rweldon@cullinantx.com References 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. Last accessed: January 2025. 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. Last accessed: May 2025

Priority ReviewBreakthrough TherapyNDAASCOClinical Study

100 Deals associated with Zipalertinib

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
EGFR ex20ins mutation in non-small cell lung cancer	NDA/BLA	United States	Taiho Pharmaceutical Co., Ltd.	28 Nov 2025
Non-small cell lung cancer stage IIIA	Phase 3	United States	Taiho Oncology, Inc.	22 Dec 2025
Non-small cell lung cancer stage IIIA	Phase 3	Japan	Taiho Oncology, Inc.	22 Dec 2025
Non-small cell lung cancer stage IIIA	Phase 3	Argentina	Taiho Oncology, Inc.	22 Dec 2025
Non-small cell lung cancer stage IIIA	Phase 3	Australia	Taiho Oncology, Inc.	22 Dec 2025
Non-small cell lung cancer stage IIIA	Phase 3	Belgium	Taiho Oncology, Inc.	22 Dec 2025
Non-small cell lung cancer stage IIIA	Phase 3	Brazil	Taiho Oncology, Inc.	22 Dec 2025
Non-small cell lung cancer stage IIIA	Phase 3	Canada	Taiho Oncology, Inc.	22 Dec 2025
Non-small cell lung cancer stage IIIA	Phase 3	France	Taiho Oncology, Inc.	22 Dec 2025
Non-small cell lung cancer stage IIIA	Phase 3	Germany	Taiho Oncology, Inc.	22 Dec 2025

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05973773 (ESMO_ASIA2025)	Phase 1	EGFR ex20ins mutation in non-small cell lung cancer	176	Zipalertinib 100 mg oral twice daily (Asia pts)	svvitzkubk(izotytmgnd) = btcmkmqxhv aeqnaokfhe (fbzmtyxjnv, 23 - 45) View more	Positive	05 Dec 2025
				Zipalertinib 100 mg oral twice daily (ROW pts)	svvitzkubk(izotytmgnd) = cvwijvorgz aeqnaokfhe (fbzmtyxjnv, 27 - 47) View more
NCT05967689 (REZILIENT2, PRNewswire \| ESMO2025) Manual	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 twice daily)	-	Positive	17 Oct 2025
NCT04036682 (REZILIENT1, Company_Website) Manual	Phase 1/2	EGFR ex20ins mutation in non-small cell lung cancer EGFR Exon 20 Mutation	84	Zipalertinib 100 mg	ltctblrele(cotljmzbvc) = fcfyacdanr caxaoneapt (sechfvovpg ) View more	Positive	09 Sep 2025
				Zipalertinib 100 mg (prior amivantamab only)	ltctblrele(cotljmzbvc) = knqvmuetcu caxaoneapt (sechfvovpg ) View more
NCT05967689 (REZILIENT2, Company_Website) Manual	Phase 2	EGFR-mutated non-small Cell Lung Cancer EGFR Mutation	40	Zipalertinib 100 mg	dbujbbsokv(egiqojwhoo) = jcddqqmhjd ungvxrwvnp (khuoyebtmu ) View more	Positive	09 Sep 2025
				Zipalertinib 100 mg (treatment-naïve)	dbujbbsokv(egiqojwhoo) = cflnixqwsm ungvxrwvnp (khuoyebtmu )
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	gpknyyqjcb(cwnnuvzxfu) = dwucvsgyeu oeorvtjabl (muhewngfvb, 16.6 - 46.5) View more	Positive	09 Sep 2025
				Zipalertinib 100 mg orally twice daily (treatment-naïve patients)	gpknyyqjcb(cwnnuvzxfu) = hgzpxaqocw oeorvtjabl (muhewngfvb, 24.5 - 91.5)
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	avhfxkubcj(mainvkarao) = weilatzfcq esjfpxxghm (rtevesfnjq, 28.2 - 42.8) View more	Positive	01 Jun 2025
				Platinum-based chemotherapy without ex20ins-targeted therapy	avhfxkubcj(mainvkarao) = omtfoqjxzp esjfpxxghm (rtevesfnjq ) View more
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	yuhdetgbxy(snqwbleoal) = memxqwfluc tejhxmldum (zvcgptxmxr ) View more	Positive	30 May 2025
				zipalertinib 100mgzipalertinib 100mg+platinum-based chemotherapy +amivantamab	yuhdetgbxy(snqwbleoal) = tawlfzppxn tejhxmldum (zvcgptxmxr ) View more
NCT04036682 (REZILIENT1, PRNewswire) Manual	Phase 2	EGFR ex20ins mutation in non-small cell lung cancer Second line EGFR Exon 20 Insertion	-	Zipalertinib	fjlgjqcwzs(fkzfkoxylc) = met its primary endpoint of overall response rate abiingrgwm (lszhkbbnfo ) 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)	nsmphpevrh(tngpvvtheu) = cznrcydtky putpwqajjq (apgiviruae, 28.2 - 42.8) View more	Positive	28 Jan 2025
				Zipalertinib 100 mg BID (prior plt-chemo)	nsmphpevrh(tngpvvtheu) = tttfiggwuf putpwqajjq (apgiviruae, 31.3 - 49.1) View more
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	vbbyatqbfh(eekoedrpqe) = nqiyhnapdj gfleuiadoe (pjtvmuxymh )	Positive	07 Dec 2024

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