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

Translational preclinical evaluation of zipalertinib in an amivantamab-resistant EGFR exon 20 insertion NSCLC model (ESMO 2025) - No abstract available

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

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

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) - No abstract available

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

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

Zipalertinib in NSCLC harboring EGFR exon 20 insertion mutations (PRNewswire) - P1/2b | N=284 | REZILIENT1 (NCT04036682) | Sponsor: Cullinan Therapeutics Inc. | "The Phase 2b REZILIENT1 study of zipalertinib monotherapy in patients with NSCLC harboring the EGFR exon 20 insertion mutations who have received prior therapy met its primary endpoint of overall response rate. The overall efficacy population (n=176) consisted of all patients who received at least one dose of 100 mg zipalertinib at data cutoff in December 2024. Patients had received a median of two prior therapies, and 38.6% of patients had a history of brain metastases. With median follow-up of 9.3 months, zipalertinib demonstrated: Among all patients treated, zipalertinib demonstrated a confirmed overall response rate (cORR) of 35.2%, with a median duration of response (mDOR) of 8.8 months. In patients who had received previous chemotherapy only (n=125), the cORR was 40.0%. Among patients with brain metastases, the systemic cORR was 30.9%."

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

Zipalertinib (EGFR ex20ins inhibitor) (GlobeNewswire) - "Pending discussions with the U.S. Food and Drug Administration, Taiho plans to submit an NDA in relapsed/refractory EGFR ex20ins NSCLC in the second half of 2025. Taiho continues enrollment of the pivotal study REZILIENT3 in 1L EGFR ex20ins NSCLC."

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

Taiho Oncology to Share Data in Five Presentations, Including Two Oral Presentations, at the 2025 American Society of Clinical Oncology Annual Meeting (PRNewswire) - "The oral presentations will feature data regarding ASTX727 (oral decitabine-cedazuridine), an agent approved for myelodysplastic syndromes (MDS), paired with venetoclax for the treatment of acute myeloid leukemia (AML) and the novel investigational drug candidate zipalertinib for the treatment of non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations. The company will also share data on three real-world studies of two FDA-approved therapies: trifluridine and tipiracil paired with bevacizumab for the later-line treatment of adult patients with metastatic colorectal cancer and futibatinib for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma."

EGFR exon 20 • P2 data • Real-world • Acute Myelogenous Leukemia • Cholangiocarcinoma • Colorectal Cancer • Myelodysplastic Syndrome • Non Small Cell Lung Cancer

Antitumor activity of YH42946, a potent tyrosine kinase inhibitor, in NSCLC harboring EGFR exon 20 insertion mutations (AACR 2025) - "It demonstrated superior activity compared to Mobocertinib (IC50 < 30 nM for ASV and IC50 < 30 nM for SVD), Furmonertinib (IC50 < 100 nM for ASV and IC50 < 100 nM for SVD), and Zipalertinib (IC50 < 100 nM for ASV and IC50 < 100 nM for SVD), and was comparable to Poziotinib (IC50 < 10 nM for ASV and IC50 < 10 nM for SVD). YH42946 is a potent small-molecule inhibitor that selectively targets EGFR ex20ins while sparing EGFR WT in preclinical models, offering potential therapeutic benefits for NSCLC patients with EGFR ex20ins mutations. Additionally, YH42946 has demonstrated effective inhibition of the EGFR pathway. Given these robust activities against EGFR ex20ins, YH42946 is anticipated to provide a significant therapeutic option for NSCLC patients harboring EGFR ex20ins mutations."

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

Cullinan Therapeutics to Present Results from REZILIENT1, a Phase 1/2 Trial of Zipalertinib in Patients with Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations Who Have Received Prior Therapy, at ASCO 2025 (GlobeNewswire) - "Cullinan Therapeutics, Inc...today announced that results from the REZILIENT1 study of zipalertinib in non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations (ex20ins) who have received prior therapy will be presented in an oral abstract session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting taking place in Chicago from May 30–June 3, 2025. The data will include results from the Phase 2b portion of the study, which explored zipalertinib monotherapy in patients with advanced or metastatic EGFR ex20ins NSCLC who progressed after prior treatment with platinum-based chemotherapy with or without amivantamab and other ex20ins-targeted therapies."

P2b data • Non Small Cell Lung Cancer

Novel strategies for rare oncogenic drivers in non-small-cell lung cancer: An update from the 2024 Annual ESMO meeting. (PubMed, Lung Cancer) - "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...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...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...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..."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

REZILIENT1: A Phase 1/2 Trial of CLN-081 in Patients with Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=284 | Active, not recruiting | Sponsor: Cullinan Therapeutics Inc. | Trial completion date: Dec 2024 ➔ Mar 2026 | Trial primary completion date: Dec 2024 ➔ Jan 2026

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • 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=160 | Recruiting | Sponsor: Taiho Oncology, Inc. | Active, not recruiting ➔ Recruiting | Trial completion date: Oct 2025 ➔ Aug 2026 | Trial primary completion date: Jun 2025 ➔ Feb 2026

Enrollment open • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Cullinan Therapeutics Provides Corporate Update and Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - Zipalertinib (EGFR ex20ins inhibitor): In January 2025, Cullinan announced that the pivotal Phase 2b portion of REZILIENT1 met the primary endpoint of overall response rate in patients with EGFR ex20ins NSCLC who have received prior therapy. The full results will be submitted for presentation at an upcoming international medical conference and shared mid-year 2025. Pending discussions with the U.S. FDA, Taiho and Cullinan plan to submit for U.S. regulatory approval in the second half of 2025."

FDA filing • P2b data • Lung Cancer • Non Small Cell Lung Cancer