zipalertinib (CLN-081) / Cullinan Therap, Otsuka, ZAI Lab - LARVOL DELTA

Efficacy of zipalertinib in Asian patients with EGFR exon 20 insertion mutated (Ex20ins) advanced non-small cell lung cancer (NSCLC) (ESMO Asia 2025) - P3 | "Here we report on the efficacy and safety of zipalertinib in pts from Asia vs the rest of world (ROW). Pts who have progressed on chemotherapy with or without prior amivantamab (including those with amivantamab and other ex20ins target therapy, such as mobocertinib) were treated with zipalertinib at 100 mg oral twice daily. Zipalertinib demonstrated similarly meaningful clinical benefit in pts from Asia and ROW. Zipalertinib was likewise tolerable and demonstrated a manageable safety profile in both groups."

Clinical • EGFR exon 20 • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

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 EGFR Exon 20 Insertion Mutations (PRNewswire) - "The NDA submission is based on the primary efficacy data from the REZILIENT1 trial..."

EGFR exon 20 • FDA filing • Non Small Cell Lung Cancer

Zipalertinib With Carboplatin and Pemetrexed for the Treatment of Resectable, Stage II-IIIB, Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=16 | Not yet recruiting | Sponsor: Jonsson Comprehensive Cancer Center

New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

REZILIENT3 (REsearching ZIpaLertinib In Egfr Non-small Cell Lung Cancer Tumors) (clinicaltrials.gov) - P3 | N=272 | Recruiting | Sponsor: Taiho Oncology, Inc. | Trial completion date: Aug 2026 ➔ May 2027 | Trial primary completion date: Jul 2026 ➔ Oct 2026

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Zipalertinib: Regulatory filing in US for NSCLC in FY 2025 (Otsuka) - Q3 FY2025 Results

FDA filing • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Translational preclinical evaluation of zipalertinib in an amivantamab-resistant EGFR exon 20 insertion NSCLC model (ESMO 2025) - "This translational study provides a mechanistic rationale for sequential use of zipalertinib in patients progressing on amivantamab. Legal entity responsible for the study Taiho Pharmaceutical Co., LTD."

EGFR exon 20 • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • TGFB1

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 (ESMO 2025) - P2 | "Conclusions In summary, zipalertinib demonstrated clinically meaningful intracranial antitumor activity in patients with NSCLC harboring ex20ins/other uncommon EGFR mt, similar to the overall systemic anticancer activity in this population, with no new safety signals observed. Cohort enrollment is ongoing to better characterize clinical activity of zipalertinib against CNS lesions."

Clinical • EGFR exon 20 • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Determination of Zipalertinib Using LC-ESI-MS/MS and Application to Pharmacokinetic Study in Mice. (PubMed, Biomed Chromatogr) - "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. 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."

Journal • PK/PD data • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

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 (PRNewswire) - "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."

EGFR exon 20 • P2b data • Non Small Cell Lung Cancer

Poziotinib for EGFR exon 20-insertion NSCLC: Clinical efficacy of the phase 2 ZENITH trial and differential impact of EGFR exon 20 insertion location on sensitivity. (PubMed, Nat Commun) - P1/2, P2 | "In vitro studies show that afatinib, poziotinib, and zipalertinib more potently inhibited near-loop than far-loop insertions, whereas mobocertinib has similar IC50 in both groups. In comparison, in the previously published EXCLAIM trial (NCT02716116), mobocertinib demonstrates similar activities across both groups in tumor size reduction (-38.5% vs. -34.1%, p = 0.59) and PFS (12.0 vs. 13.0 months, p = 0.99). Therefore, EGFRex20ins location differentially impacts the sensitivity of TKIs."

Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Phase 2 Interim Results of Zipalertinib in Patients With NSCLC Harboring Uncommon Non-Exon 20 Insertion EGFR Mutations (IASLC-WCLC 2025) - P2 | "The safety profile of zipalertinib was manageable, with no new safety signals. Enrollment in this study is ongoing, focusing on previously untreated patients to confirm the observed preliminary clinical efficacy."

Clinical • P2 data • Anemia • Dental Disorders • Dermatitis • Dermatology • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Stomatitis • EGFR

Zipalertinib in NSCLC Patients (Pts) With EGFR Exon 20 Insertion (Ex20Ins) Mutations Who Received Prior Amivantamab (IASLC-WCLC 2025) - "Mature efficacy data, including at least 9 months follow up for all 83 pts will be presented. Conclusions : Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in pts with exon20ins NSCLC who have received prior chemotherapy and prior amivantamab, reflecting a clinically-relevant patient population for which there are currently no approved therapies."

Clinical • EGFR exon 20 • Anemia • Dental Disorders • Dermatitis • Dermatology • Hematological Disorders • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Pneumonia • Pruritus • Solid Tumor • Stomatitis • EGFR

Authors reported results from the REZILIENT2 study of zipalertinib from the cohort of patients with NSCLC harboring uncommon non-exon 20 insertion EGFR mutations2 (PRNewswire) - "In the overall efficacy population (n=40), confirmed ORR was 30% with a mDOR of 7.75 months, and the disease control rate (DCR) was 70%. In the treatment-naïve population (n=8), ORR was significantly higher (62.5%) compared to the previously treated patient population (n=32, ORR 21.9%)."

P2b data • Non Small Cell Lung Cancer

Authors reported results from the REZILIENT1 study of zipalertinib from the cohort of NSCLC patients with EGFR ex20ins mutations who received prior amivantamab therapy (PRNewswire) - "With follow-up of more than 9 months, zipalertinib demonstrated: In all patients (n=84), confirmed objective response rate (ORR) was 27.4% with median duration of response (mDOR) of 8.5 months, and the disease control rate (DCR) was 84.5%. In patients with prior amivantamab only (n=54), ORR was 31.5% with mDOR of 9.5 months, and the DCR was 87.0%. In patients with prior amivantamab and other ex20ins-targeted therapy (n=30), ORR was 20.0% with mDOR of 8.3 months, and the DCR was 80.0%."

P1/2 data • Non Small Cell Lung Cancer

REZILIENT4: A Study to Assess the Efficacy and Safety of Zipalertinib Versus Placebo for Adjuvant Treatment in Participants With Stage IB-IIIA NSCLC With Uncommon EGFR Mutations, Following Complete Tumor Resection (clinicaltrials.gov) - P3 | N=360 | Recruiting | Sponsor: Taiho Oncology, Inc.

New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Zipalertinib: Completion of P3 REZILIENT3 trial (NCT05973773) for 1L NSCLC in Aug 2026 (Otsuka) - Q2 FY2025 Results: Completion of P2 REZILIENT2 trial (NCT05967689) for Exon 2 NSCLC in Aug 2026

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Zipalertinib: Launch for 2L NSCLC in 2026 (Otsuka) - Q2 FY2025 Results: Regulatory filing for 1L NSCLC in 2027

Filing • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Taiho Oncology Announces Acceptance of Abstract for Zipalertinib at the ESMO Congress 2025 (PRNewswire) - "Taiho Oncology...announced it will present new data from the REZILIENT2 trial of zipalertinib at the European Society for Medical Oncology (ESMO) Congress 2025....The abstract accepted for a mini oral presentation includes the preliminary efficacy and safety data from the Phase 2b REZILIENT2 trial of zipalertinib, an oral, highly selective, irreversible EGFR tyrosine kinase inhibitor (TKI), in patients with advanced or metastatic NSCLC harboring EGFR ex20ins mutations or EGFR uncommon non-ex20ins mutations and active brain metastases and/or leptomeningeal disease....Full abstract details will be available via the conference website at 12:05 CEST a.m. on Oct. 13, 2025."

EGFR exon 20 • P2b data • Non Small Cell Lung Cancer

Taiho Oncology and Cullinan Therapeutics Announce Acceptance of Abstracts for Zipalertinib at the IASLC 2025 World Conference on Lung Cancer (Taiho Press Release) - "Taiho Oncology, Inc., and Cullinan Therapeutics...announced the presentation of new data from zipalertinib REZILIENT1 and REZILIENT2 trials at the International Association of the Study of Lung Cancer’s (IASLC) 2025 World Conference on Lung Cancer (WCLC)....The abstracts accepted for mini oral presentations include updated efficacy and safety data from the Phase 2b REZILIENT1 trial, focusing on patients with EGFR ex20ins NSCLC previously treated with amivantamab, as well as the preliminary efficacy and safety results from the Phase 2 parallel cohort REZILIENT2 trial in patients with advanced or metastatic NSCLC harboring uncommon non-ex20ins EGFR mutations....Full abstract details will be available via the conference website at 1 p.m. EDT August 13, 2025."

EGFR exon 20 • P2b data • Non Small Cell Lung Cancer

Efficacy of zipalertinib in NSCLC patients with EGFR exon 20 insertion mutations who received prior platinum-based chemotherapy with or without amivantamab. (BASCO-MN 2025) - No abstract available

Clinical • EGFR exon 20 • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

NCCN Awards Grants to Improve Care for People with Non-Small Cell Lung Cancer in Collaboration with Taiho Oncology, Inc. (PRNewswire) - "The National Comprehensive Cancer Network (NCCN) Oncology Research Program...announced new funding for advancing clinical research in Non-Small Cell Lung Cancers (NSCLC). Two grants have been awarded to creative, investigator-initiated research projects to evaluate the effectiveness of zipalertinib in the treatment of NSCLC....The selected projects are: L13: Phase 2 Trial of Zipalertinib in Patients with Resectable Non-small cell lung cancer with EGFR Exon 20 Insertion or Uncommon/Compound Mutations; Adjuvant ctDNA-Adapted Personalized Treatment with Zipalertinib in Early-Stage Atypical EGFR-Mutant NSCLC (ADAPT-A)"

EGFR exon 20 • Financing • Non Small Cell Lung Cancer

Efficacy of zipalertinib in NSCLC patients with EGFR exon 20 insertion mutations who received prior platinum-based chemotherapy with or without amivantamab. (ASCO 2025) - P1/2 | "Of the 51 pts with prior ami, 30 had no other ex20ins-directed therapy, while 21 had also received other ex20ins drugs (such as mobocertinib, sunvozertinib, BLU-451, or poziotinib), the cORR was 30.0% and 14.3%, respectively. Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in pts with exon20ins NSCLC who have received prior platinum-based chemotherapy and for those who received prior amivantamab, a significant and growing unmet need. BICR assessed tumor responses per RECIST v1.1.CR=complete response, PR=partial response, SD=stable disease."

Clinical • EGFR exon 20 • IO biomarker • Anemia • Dental Disorders • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • EGFR

REZILIENT2: A Study of Zipalertinib in Patients With Advanced Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions or Other Uncommon Mutation. (clinicaltrials.gov) - P2 | N=220 | Recruiting | Sponsor: Taiho Oncology, Inc. | N=160 ➔ 220

Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Zipalertinib in Patients With EGFR Exon 20 Insertion-Positive NSCLC Previously Treated With Platinum-Based Chemotherapy With or Without Amivantamab. (PubMed, J Clin Oncol) - P1/2 | "Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in patients with EGFR ex20ins-mutant NSCLC who received prior platinum-based chemotherapy with or without amivantamab."

Journal • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • EGFR

Taiho Oncology and Cullinan Therapeutics Announce Pivotal REZILIENT1 Phase 1/2 Data Published in the Journal of Clinical Oncology (PRNewswire) - P1/2b | N=284 | REZILIENT1 (NCT04036682) | Sponsor: Cullinan Therapeutics Inc. | "Highlights of the REZILIENT1 Phase 1/2 trial in the authors' conclusions include: Zipalertinib demonstrated clinically meaningful efficacy in the primary efficacy population (n=176), including 51 patients who had received prior amivantamab; The confirmed objective response rate (ORR) was 35.2% overall, and median duration of response (mDOR) and progression-free survival were 8.8 months and 9.4 months, respectively; In patients treated after prior platinum-based chemotherapy only (n=125), ORR was 40% with mDOR of 8.8 months; The safety profile of zipalertinib was manageable and consistent with previously reported data."

EGFR exon 20 • P1/2 data • Non Small Cell Lung Cancer