Zorifer (zorifertinib) / Alpha Biopharma, AstraZeneca - LARVOL DELTA

Randomized phase 3 study of first-line AZD3759 (zorifertinib) versus gefitinib or erlotinib in EGFR-mutant (EGFRm+) non–small-cell lung cancer (NSCLC) with central nervous system (CNS) metastasis. (ASCO 2023) - P2/3 | "First-line AZD3759 demonstrated superior systemic and IC antitumor efficacy compared with first generation EGFR TKIs in pts with EGFRm+ NSCLC and CNS metastasis. Adverse events were as expected and manageable. IC antitumor activity."

Clinical • P3 data • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Efficacy and Safety of Zorifertinib Combined with Double-Dose Furmonertinib and Pemetrexed Intrathecal Chemotherapy in Treating EGFR-Mutant Non-Small Cell Lung Cancer with Leptomeningeal Metastasis: A Single-Arm, Prospective Clinical Study (ChiCTR) - P=N/A | N=60 | Not yet recruiting | Sponsor: Nanjing Drum Tower Hospital; Nanjing Drum Tower Hospital

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

Material Balance of [14C]Zorifertinib in Healthy Adult Male Participants in China (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Alpha Biopharma (Jiangsu) Co., Ltd. | Recruiting ➔ Completed

Trial completion • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A prospective clinical study evaluating the pharmacokinetics, safety, and preliminary efficacy of zorifertinib (AZD3759) combined with third-generation EGFR-TKIs in EGFR-mutant positive NSCLC patients with leptomeningeal progression after third-generation EGFR-TKI resistance (ChiCTR) - P=N/A | N=30 | Not yet recruiting | Sponsor: West China Hospital of Sichuan University; West China Hospital of Sichuan University

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

Material Balance of [14C]Zorifertinib in Healthy Adult Male Participants in China (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Alpha Biopharma (Jiangsu) Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Zorifertinib With Osimertinib for NSCLC With Meningeal Progression (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Alpha Biopharma (Jiangsu) Co., Ltd. | Not yet recruiting ➔ Recruiting

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

Material Balance of [14C]Zorifertinib in Healthy Adult Male Participants in China (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Alpha Biopharma (Jiangsu) Co., Ltd.

New P1 trial • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

MATCHING-ADJUSTED INDIRECT COMPARISON AND COST-UTILITY OF ZORIFERTINIB VERSUS OSIMERTINIB IN TREATING NEWLY DIAGNOSED EGFR-MUTANT NSCLC WITH CNS METASTASES IN CHINA (ISPOR 2026) - P2/3, P3 | "From the perspective of the Chinese healthcare system, zorifertinib is a cost-effective treatment for newly diagnosed EGFRm+ NSCLC patients with CNS metastases compared with osimertinib, which provided patients with an effective and cost-saving treatment option."

HEOR • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

Zorifertinib Plus Intra-Ommaya CSF Chemotherapy for Leptomeningeal Progression in NSCLC After Third-Generation EGFR-TKI (clinicaltrials.gov) - P2 | N=38 | Not yet recruiting | Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

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

A Real-World Study Evaluating the Efficacy and Safety of Zorifertinib in Patients with NSCLC and Leptomeningeal Metastases after Resistance to Third-Generation EGFR-TKIs: A Bidirectional, Non-Interventional, Observational, Multicenter Study (ChiCTR) - P=N/A | N=120 | Sponsor: Nanjing Brain Hospital; Nanjing Brain Hospital

New trial • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Zorifertinib Plus Radiotherapy as First-Line Treatment in EGFR-Mutant NSCLC with Brain Metastases: A Prospective Clinical Study (ChiCTR) - P4 | N=38 | Recruiting | Sponsor: Chongqing University Cancer Hospital; Chongqing University Cancer Hospital

New P4 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A palmitoylation-related prognostic risk scoring model and tumor microenvironment characterization in lung adenocarcinoma, using single-cell RNA sequencing data. (PubMed, Comput Biol Chem) - "Our study comprehensively reveals the cellular heterogeneity of palmitoylation, establishes a robust palmitoylation-related prognostic model, and identifies SEC61G as a promising therapeutic target in LUAD, offering a novel perspective for LUAD precision stratification and treatment studies."

Biomarker • Journal • Tumor mutational burden • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • GAPDH • HLA-DRA • SEC61G • TMB

Subtype-specific APOBEC enrichment links genomic instability to predict immunotherapy response in breast cancer subtypes. (PubMed, Int J Biol Macromol) - "Based on in vivo experiments in mice, our research highlights that the administration of specific agents-AZD3759 for HER2+, Vorinostat for TNBC, and SGC0946 for Luminal-when combined with anti-PD-1 therapy, not only boosts therapeutic effectiveness but also transforms the immunological environment within tumors. This synergistic approach led to notable reductions in tumor volume and an increase in cytotoxic T cell density in in vivo and in vitro experiments, further validating the role of AMrs scores in tailoring treatment modalities across BRCA subtypes. Overall, our study elucidates the critical role of APOBEC family genes in BRCA heterogeneity, highlighting their potential as biomarkers for personalized therapeutic approaches and pointing towards future research directions in integrating APOBEC-related mechanisms with immunotherapy."

IO biomarker • Journal • Tumor mutational burden • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • HER-2 • TMB

Identification of Poor Prognosis-Associated Fibroblast Subpopulation Signature Genes Utilizing the Scissor Algorithm to Classify Colorectal Cancer Subtypes and Evaluate the Immune Landscape. (PubMed, Gut Liver) - "Drug sensitivity predictions suggested that patients with this cell subtype may respond better to specific anticancer agents (e.g., AZD3759, Erlotinib, Gefitinib). Moreover, their predictive value in CRC therapy was revealed. The study provided new perspectives for CRC prognosis evaluation and personalized immune-targeted combination therapies."

Journal • Colorectal Cancer • Oncology • Solid Tumor • SPP1

Epidermal growth factor receptor tyrosine kinase inhibitor for the treatment of non-small cell lung cancer in the past 30 years (1997-2026). (PubMed, Chin Med J (Engl)) - "Since 1997, EGFR tyrosine kinase inhibitors (EGFR-TKIs) have evolved from first-generation agents, such as gefitinib, erlotinib, and icotinib, to second-generation agents like afatinib and dacomitinib, now to third-generation agents, including osimertinib, aumolertinib, furmonertinib, befotertinib, rezivertinib, rilertinib, limertinib, lazertinib, mifanertinib for EGFR L858R, sunvozertinib for EGFR exon 20 insertion (20ins), and zorifertinib for EGFR-sensitive mutation with brain metastases. Over the past 30 years, substantial advancements have been made in the comprehensive management of EGFR-mutant NSCLC. This systemic review provides the history of the development of EGFR-TKI therapy for NSCLC from 1997 to 2026, highlighting clinical milestones, emerging therapies, and future directions in this rapidly evolving field."

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

A Prospective Cohort Study of Zorifertinib as a First-line Treatment in Patients With Epidermal Growth Factor Receptor-mutant Advanced Non-small Cell Lung Cancer With Central Nervous System (CNS) Metastases (clinicaltrials.gov) - P=N/A | N=800 | Recruiting | Sponsor: Alpha Biopharma (Jiangsu) Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Zorifertinib With Osimertinib for NSCLC With Meningeal Progression (clinicaltrials.gov) - P1 | N=42 | Not yet recruiting | Sponsor: Alpha Biopharma (Jiangsu) Co., Ltd.

New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A real-world, prospective clinical study of zorifertinib combined with furmonertinib in leptomeningeal metastases patients with EGFR mutation-positive NSCLC and third-generation EGFR-TKIs resistance (ChiCTR) - P2 | N=29 | Not yet recruiting | Sponsor: Nanjing Brain Hospital; Nanjing Brain Hospital

New P2 trial • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Immunogenic cell death-related genes as prognostic biomarkers and therapeutic insights in uterine corpus endometrial carcinoma: an integrative bioinformatics analysis. (PubMed, Front Oncol) - "Finally, we found that hyper-immunogenicity may be sensitive to immunotherapy and certain drugs (AZD5991, Ibrutinib, Osimertinib, AGI-5198, Savolitinib, Sapitinib, AZ960, AZD3759 and Ruxolitinib), while PCI-34051 and Vorinostat showed sensitivity in patients with hypo-immunogenicity. Our results demonstrate that ICD plays an important role in UCEC progression, suggesting that ICD-related markers could serve as potential targets for prognosis and treatment."

Biomarker • IO biomarker • Journal • Tumor mutational burden • Endometrial Cancer • Oncology • Solid Tumor • Uterine Cancer • CD52 • STAT1 • TMB

A Prospective Cohort Study of Zorifertinib as a First-line Treatment in Patients With Epidermal Growth Factor Receptor-mutant Advanced Non-small Cell Lung Cancer With Central Nervous System (CNS) Metastases (clinicaltrials.gov) - P=N/A | N=800 | Not yet recruiting | Sponsor: Alpha Biopharma (Jiangsu) Co., Ltd.

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

Structure-Property Relationships Reported for the New Drugs Approved in 2024. (PubMed, Mini Rev Med Chem) - "The analysis focused on aprocitentan, flurpiridaz F-18, inavolisib, vorasidenib, ensitrelvir, golidocitinib, and zorifertinib, highlighting the key structural modifications that enhanced their drug-like properties. When developing central nervous system-penetrant drugs such as zorifertinib, careful control of rotatable bonds, hydrogen bond donors, and molecular lipophilicity was critical for optimizing blood-brain barrier penetration while remaining suitable for oral administration. These findings on structureproperty relationships offer valuable guidance for future drug development, particularly in addressing challenges related to solubility, bioavailability, and tissue-specific drug distribution."

Journal

Comparing the Effectiveness and Safety of First-line Interventions in Patients With Advanced Epidermal Growth Factor Receptor-mutant Non-small Cell Lung Cancer, With Particular Focus on Brain Metastatic Status: A Systematic Review and Network Meta-analysis. (PubMed, Clin Oncol (R Coll Radiol)) - "In EMAN patients, osimertinib + CT and amivantamab + lazertinib were associated with optimal PFS and OS, respectively. Among BM patients, osimertinib + CT offered the best PFS benefits. These findings may assist in clinical decision-making and personalized care for EMAN and BM patients. The study is registered on PROSPERO (CRD42024506995)."

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

The climb toward intracranial efficacy: Zorifertinib in EGFR-mutant NSCLC with CNS metastases in the EVEREST trial. (PubMed, Med) - "The phase III EVEREST trial evaluating zorifertinib in the treatment of metastatic EGFR-mutant NSCLC was groundbreaking in its specific inclusion of patients with brain metastases.1 Zorifertinib prolonged systemic and intracranial progression-free survival compared with first-generation EGFR inhibitors, yet questions remain about its efficacy and toxicity compared with osimertinib."

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

Alpha Biopharma received NMPA approval for Zorifertinib Tablets (Zorifer), the world's first EGFR-TKI for lung cancer with brain metastases (PRNewswire) - "On November 20, 2024, the National Medical Products Administration (NMPA) announced on its official website that the NMPA approved the listing of Zorifertinib Hydrochloride Tablets (trade name: Zorifer), a Class 1 innovative drug, developed by Alpha Biopharma. This product is indicated for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) accompanied with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) substitution mutation and central nervous system (CNS) metastases....The EVEREST trial, an international multi-center randomized controlled phase III trial of Zorifertinib, demonstrated its superior ability to control intracranial lesions."

China approval • Non Small Cell Lung Cancer

First-line zorifertinib for EGFR-mutant non-small cell lung cancer with central nervous system metastases: The phase 3 EVEREST trial. (PubMed, Med) - P2/3 | "Zorifertinib significantly improved systemic and intracranial PFS versus first-generation EGFR-TKIs; adverse events were manageable. Sequential use of zorifertinib and third-generation EGFR-TKIs showed the potential to prolong patients' survival. The results favor zorifertinib as a novel, well-validated first-line option for CNS-metastatic patients with EGFR-mutant NSCLC."

Journal • P3 data • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR