Zegfrovy (sunvozertinib) / Dizal Pharmaceutical, AstraZeneca - LARVOL DELTA

Sunvozertinib Plus Anlotinib as First-Line Treatment for NSCLC With EGFR Sensitive Mutations and Co-Mutations: Updated Phase II Data (IASLC-WCLC 2026) - "Conclusions : Sunvozertinib combined with anlotinib continues to demonstrate robust antitumor activity and a manageable safety profile as first-line treatment for EGFR-mutant NSCLC with high-risk co-mutations. The high 12-month PFS rate suggests that this all-oral combination regimen provides a promising treatment option for patient population that typically derives suboptimal benefit from standard TKI monotherapy."

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR • TP53

Concurrent icotinib and definitive radiotherapy followed by detection of an EGFR exon 20 insertion at disease progression in unresectable stage III EGFR S768I-mutant lung adenocarcinoma: a case report. (PubMed, Front Oncol) - "Subsequent treatment with afatinib, ivonescimab plus chemotherapy, and sunvozertinib was selected according to dynamic molecular profiling. More importantly, it highlights the value of repeat biopsy and comprehensive genomic profiling for interpreting molecular changes at disease progression and guiding subsequent individualized treatment in patients with uncommon EGFR mutations. However, these observations are derived from a single case and require validation in larger prospective studies."

Journal • Lung Adenocarcinoma • Lung Cancer • Mucositis • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • EGFR

Sunvozertinib monotherapy versus platinum-based chemotherapy as first-line treatment for advanced NSCLC with EGFR exon20ins: Primary analysis of a multinational phase 3 randomized study (WU-KONG28). (ASCO 2026) - P1/2, P2, P3 | " Eligible patients were randomized in a 1:1 ratio, stratified by baseline brain metastasis status, to receive either sunvozertinib 300 mg once daily or chemotherapy (carboplatin [AUC5] and pemetrexed [500 mg/m²]) once every 3 weeks for up to 6 cycles, followed by pemetrexed maintenance therapy until disease progression or other discontinuation criteria were met. Sunvozertinib demonstrated significantly superior antitumor efficacy than chemotherapy with a manageable safety profile. These results support sunvozertinib as a first-line treatment for advanced NSCLC harboring EGFR exon20ins."

Clinical • EGFR exon 20 • Late-breaking abstract • Metastases • Monotherapy • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

Operationalizing the PMMR Standardized Framework to Manage Patients on TKIs for Non-Small Cell Lung Cancer (NSCLC) (IASLC-WCLC 2026) - "Firstly, TA AE data was collected (Osimertinib, Amivantamab-Lazertinib, Sunvozertinib, Crizotinib, Alectinib, Afatinib, Entrectinib, Selpercatinib, Lorlatinib) based on clinical trial data, regulatory drug labels, and provincial/national guidelines. Details, including barrier and facilitators, and recommendations on implementation will be presented at the conference. Conclusions : To further enhance adherence and treatment efficacy, future directions include: (i) integrating a grading criterion for nurses in the EMR while using the scripts to enhance assessment and (ii) creating a remote monitoring application that leverages PMMR."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

P-Loop/αC-Helix Compressing Mutations and Exon 20 Insertions in EGFR-Mutant NSCLC: A Rapidly Evolving Therapeutic Landscape. (PubMed, J Clin Oncol) - "EGFR PACC and ex20ins are established subgroups of kinase domain mutations, distinct from classical mutations, due to structure and responsiveness to available TKIs."

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

Efficacy and Safety of Sunvozertinib as Adjuvant Treatment in Resected Stage IB-IIIB EGFR Exon 20 Insertion Mutated NSCLC (IASLC-WCLC 2026) - P2 | "The long-term survival benefits still require final assessment upon completion of patient enrollment and with longer-term follow-up. This study provides preliminary evidence to support the exploration of postoperative adjuvant targeted therapy for this specific patient population."

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

A multinational pivotal study of sunvozertinib in platinum pretreated non-small cell lung cancer with EGFR exon 20 insertion mutations: Primary analysis of WU-KONG1 study. (ASCO 2024) - P1/2 | "All patients received prior platinum-based chemotherapy for advanced NSCLC, and 43.4% and 13.3% had prior onco-immunotherapy or amivantamab treatment. In this primary analysis of WU-KONG1 multinational pivotal study, sunvozertinib demonstrated promising antitumor efficacy in platinum pre-treated NSCLC with EGFR exon20ins, with a tolerable safety profile. The updated data will be presented at the meeting."

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

Genetic biomarker study of sunvozertinib for clinical prognosis and prediction in NSCLC with EGFR exon 20 insertion mutation. (PubMed, Cell Rep Med) - "Acquired EGFR C797S is identified as a potential on-target resistance mutation to sunvozertinib. Finally, efforts are undertaken to investigate therapeutic approaches that aim to overcome the putative acquired resistance to sunvozertinib."

Biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Multicentre Retrospective Study on Efficacy and Safety of Novel EGFR-TKIs in Advanced EGFR Ex20ins NSCLC (CTONG 2401 Study) (IASLC-WCLC 2026) - "89 patients received prior chemotherapy prior to TKI, while no patients received prior amivantamab. Conclusions : This represents the largest real-world dataset on patients with advanced EGFR ex20ins NSCLC treated with novel EGFR ex20ins active TKIs. We confirm the clinical activity of sunvozertinib and furmonertinib across different treatment lines, providing valuable evidence to support their clinical application in this population."

EGFR exon 20 • Metastases • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

Assessing an Oral EGFR Inhibitor, DZD9008 in Patients With Advanced Non-small Cell Lung Cancer(NSCLC) With EGFR Mutations (WU-KONG15) (clinicaltrials.gov) - P=N/A | N=180 | Recruiting | Sponsor: Peking Union Medical College Hospital | Trial completion date: Jun 2026 ➔ Jun 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2026

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

Sunvozertinib as first-line treatment in NSCLC patients with EGFR Exon20 insertion mutations (ESMO 2023) - P=N/A, P1/2, P2, P3 | "Conclusions In the 1st line setting, sunvozertinib as monotherapy demonstrated promising anti-tumor efficacy and acceptable safety profile in NSCLC patients with EGFR exon20ins. A phase III, multinational, randomized study (WU-KONG28, NCT05668988) is ongoing to compare sunvozertinib to chemotherapy as 1st line treatment for EGFR exon20ins NSCLC."

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

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

A Retrospective, Multi-Cohort Study of EGFR Exon 20 Insertion Mutations in Non-Small Cell Lung Cancer (IASLC-WCLC 2026) - "In the medical treatment cohort (n=24), patients were categorized into three groups based on first-line or later-line treatment regimens: (1) novel EGFR-ex20ins targeted therapies (e.g. sunvozertinib), (2) conventional EGFR-TKIs (e.g. furmonertinib), and (3) chemotherapy-based regimens (with or without immunotherapy/anti-angiogenesis). Novel targeted therapies showed numerically longer PFS than chemotherapy, though the difference was not statistically significant. These findings highlight the need for individualized risk stratification and further research to optimize treatment sequencing in this molecular subtype."

EGFR exon 20 • IO biomarker • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • EGFR • MET

Sunvozertinib in NSCLC Patients with EGFR Exon20 Insertion Mutations (IASLC-NACLC 2022) - P1/2 | "The data suggest sunvozertinib is active in both treatment naïve and prior platinum-based chemo treated NSCLC patients with EGFR Exon20ins. as well as in patients with CNS metastasis. Two pivotal studies (NCT03974022 and China CTR20211009) are ongoing and the updated data will be presented at the meeting."

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

Sunvozertinib Plus Anlotinib as First-Line Treatment for NSCLC With EGFR Sensitive Mutations and Co-Mutations: Updated Phase II Data [Google translation] (IFENG.COM) - "Results showed that in 23 evaluable patients, the confirmed objective response rate (ORR) was 69.6%, and the disease control rate (DCR) was 91.3%; the median follow-up was 10.4 months, and the estimated 12-month progression-free survival (PFS) rate was 83.8%. Overall safety was manageable, with common ≥ grade 3 treatment-related adverse events including diarrhea, anemia, and elevated creatine phosphokinase."

P2 data • Non Small Cell Lung Cancer

A Multinational Phase 2 Randomized Pivotal Study of Sunvozertinib in Pretreated NSCLC With EGFR Exon 20 Insertion Mutations (IASLC-WCLC 2025) - P1/2 | "Overall, 300 mg once daily showed more favorable clinical outcomes, especially for patients with prior amivantamab treatment or baseline brain metastasis. Detailed data will be presented at the conference."

Clinical • EGFR exon 20 • P2 data • Anemia • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 20 Insertion Mutations (WU-KONG1B). (PubMed, J Clin Oncol) - P1/2 | "Sunvozertinib is efficacious at both 200 and 300 mg once daily in treating platinum-pretreated patients with advanced EGFR exon20ins NSCLC. The treatment-related adverse events of sunvozertinib were consistent with an EGFR tyrosine kinase inhibitor, with a more favorable safety profile at 200 mg than 300 mg once daily."

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

Sunvozertinib for the treatment of NSCLC with EGFR Exon20 insertion mutations: The first pivotal study results. (ASCO 2023) - P1/2, P2 | "The first pivotal study results confirmed sunvozertinib’s superior anti-tumor efficacy than the current available therapy for NSCLC with EGFR exon20ins. The safety profile from WU-KONG6 study was consistent with previously reported findings. The updated data will be presented at the meeting."

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

Study of Oral EGFR Inhibitor DZD6008 Combined With Sunvozertinib in Patients Who Have Advanced NSCLC With EGFR Mutations (TIAN-SHAN8) (clinicaltrials.gov) - P1/2 | N=220 | Recruiting | Sponsor: Dizal Pharmaceuticals | N=160 ➔ 220

Enrollment change • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

AstraZeneca completes global license agreement for oral EGFR inhibitor Zegfrovy for lung cancer (AstraZeneca Press Release) - "Through this agreement, AstraZeneca has acquired worldwide rights to develop and commercialise Zegfrovy...AstraZeneca will make an upfront payment of $600m to Dizal together with additional payments of up to $900m upon achievement of specific development, regulatory and sales-related milestones. Additionally, Dizal will receive tiered royalties on the global sales of Zegfrovy....This transaction does not impact AstraZeneca’s financial guidance for 2026."

EGFR exon 20 • Licensing / partnership • Non Small Cell Lung Cancer

Dizal to Present Emerging Data on ZEGFROVY in Non-Small Cell Lung Cancer at WCLC 2026 (PRNewswire) - "At WCLC 2026, Dizal will present the latest findings from a study evaluating ZEGFROVY as adjuvant treatment in patients with resected stage IB-IIIB EGFR exon20ins NSCLC....In addition, Dizal will report updated data from a Phase 2 study evaluating ZEGFROVY in combination with Anlotinib as first-line treatment for NSCLC with EGFR sensitizing mutations and co-mutations."

P2 data • Non Small Cell Lung Cancer

Efficacy and safety of sunvozertinib in prior platinum treated NSCLC patients with EGFR exon 20 insertion mutations: Primary analysis from the multinational WU-KONG1B pivotal study (ESMO 2024) - P1/2 | "The primary efficacy analysis set included 107 patients post platinum-based chemotherapy: 57.9% Asian, 54.2% from Asia, 25.2% with baseline brain metastasis, 13.1% with prior amivantamab, 48.6% with prior onco-immunotherapy and 13.1% with EGFR TKI treatment. The primary results of WU-KONG1B showed promising anti-tumor efficacy of sunvozertinib in advanced NSCLC with EGFR exon20ins, regardless of different subgroups. The updated results will be presented at the conference."

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

AstraZeneca enters exclusive global license agreement for novel oral EGFR inhibitor Zegfrovy for lung cancer with Dizal Pharmaceutical (AstraZeneca Press Release) - "AstraZeneca will acquire worldwide rights to develop and commercialise Zegfrovy....AstraZeneca will make an upfront payment to Dizal of $600m and additional payments of up to $900m upon achievement of specific development, regulatory and sales-related milestones. Additionally, Dizal will receive tiered royalties on the global sales of Zegfrovy. The transaction is expected to close in the second half of 2026, subject to customary closing conditions and regulatory clearances. The transaction does not impact AstraZeneca’s financial guidance for 2026."

Licensing / partnership • Non Small Cell Lung Cancer

From data mining to mechanistic prediction: a study on drug-induced lung injury integrating FAERS, machine learning, and network toxicology. (PubMed, Arch Toxicol) - "Our results highlighted MMP9 and ERBB2 as core targets associated with the pulmonary toxicity of Sunvozertinib and Zongertinib, and subsequent molecular docking and molecular dynamics simulations further suggested stable binding between the compounds and the above targets. This integrated framework enables efficient early prediction of DLI risk while providing mechanistic insights into drug-induced pulmonary toxicity. Overall, our study offers a practical and reproducible computational strategy for DLI risk assessment in drug development and supports safer clinical medication and rational drug design."

Journal • Respiratory Diseases • HER-2 • MMP9

Crystal structure of sunvozertinib, C29H35ClFN7O3, from synchrotron X-ray powder data and DFT optimization. (PubMed, Acta Crystallogr E Crystallogr Commun) - "The asymmetric unit in space group C2 contains two mol-ecules, A and B, and the crystal structure consists of alternating layers of mol-ecules A and B lying parallel to (201). O-H⋯O hydrogen bonds link the B mol-ecules into chains propagating along the b-axis direction while pairwise N-H⋯N hydrogen bonds link the A mol-ecules into dimers."

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