{ "abstract": "Background: Dirozalkib is a highly selective anaplastic lymphoma kinase (ALK) inhibitor with intracranial antitumor activity against crizotinib-resistant mutations. This phase III trial evaluated dirozalkib versus crizotinib in patients with ALK inhibitor-naïve, ALK-positive, advanced non-small-cell lung cancer (NSCLC). Methods: In this multicenter, randomized, open-label DIAMOND-2 trial, adult patients with ALK inhibitor-naïve, ALK-positive, advanced NSCLC who either had received no prior systemic therapy or had experienced disease progression or intolerance after one prior chemotherapy regimen were randomly assigned 1:1 to dirozalkib (500 mg once daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival (PFS). Results: Between 2022 January 24 and 2023 April 30, 275 patients were randomly assigned to receive dirozalkib (n = 137) or crizotinib (n = 138). As of 2025 May 31, the median follow-up durations were 32.8 and 31.6 months, respectively. Median investigator-assessed PFS was 29.5 (95% confidence interval [CI] = 20.3 to not reached) months with dirozalkib versus 12.9 (95% CI = 11.1 to 17.6) months with crizotinib (hazard ratio [HR] = 0.47, 95% CI = 0.34 to 0.66; P < 0.001). Blinded-independent-central-review-assessed PFS was also significantly prolonged with dirozalkib (median PFS, 27.5 versus 12.9 months; HR = 0.54, 95% CI = 0.39 to 0.74; P < 0.001). Grade ≥3 treatment-emergent adverse events (TEAEs) were less frequent with dirozalkib than with crizotinib (60.6% versus 72.5%), and TEAEs led to treatment discontinuation in 2.2% and 7.2% of patients, respectively. Conclusions: Dirozalkib significantly improved PFS versus crizotinib, with a manageable safety profile, supporting its use as a first-line therapy for ALK-positive advanced NSCLC. Trial registration: This trial was registered at ClinicalTrials.gov on 2022 January 24 (NCT05204628).", "abstract_shown": true, "affiliations": [ "Department of Oncology, Jilin Provincial Cancer Hospital, Changchun, Jilin, P. R. China.", "Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, P. R. China.", "Department of Thoracic Medical Oncology, The Affiliated Cancer Hospital of Harbin Medical University, Harbin, Heilongjiang, P. R. China.", "Department of Thoracic Medical Oncology, Hunan Provincial Cancer Hospital, Changsha, Hunan, P. R. China.", "Department of Medical Oncology, Yunnan Provincial Cancer Hospital, Kunming, Yunnan, P. R. China.", "Department of Respiratory and Critical Care Medicine, Nanfang Hospital Affiliated to Southern Medical University, Guangzhou, Guangdong, P. R. China.", "Department of Thoracic Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, P. R. China.", "Department of Respiratory Oncology, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi, P. R. China.", "Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P. R. China.", "Department of Respiratory Medical Oncology, The Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China.", "Department of Oncology, The Affiliated Hospital of Chengde Medical University, Chengde, Hebei, P. R. China.", "Department of Medical Oncology, Meizhou People's Hospital, Meizhou, Guangdong, P. R. China.", "Department of Clinical Science, Xuanzhu Biopharmaceutical Co. Ltd., Beijing, P. R. China." ], "article_type": "research article", "arxiv": null, "author_total": 18, "authors": [ { "affs": [ 0 ], "name": "Ying Liu" }, { "affs": [ 1 ], "name": "Xiangjiao Meng" }, { "affs": [ 2 ], "name": "Yan Yu" }, { "affs": [ 3 ], "name": "Jianhua Chen" }, { "affs": [ 4 ], "name": "Runxiang Yang" }, { "affs": [ 5 ], "name": "Laiyu Liu" }, { "affs": [ 6 ], "name": "Yanqiu Zhao" }, { "affs": [ 7 ], "name": "Ruifen Tian" }, { "affs": [ 8 ], "name": "Dianming Li" }, { "affs": [ 9 ], "name": "Ruiling Ning" }, { "affs": [ 10 ], "name": "Qingshan Li" }, { "affs": [ 11 ], "name": "Guowu Wu" }, { "affs": [ 12 ], "name": "Li Wang" }, { "affs": [ 12 ], "name": "Xianghui Duan" }, { "affs": [ 12 ], "name": "Xuejie Guo" }, { "affs": [ 12 ], "name": "Yan Hu" }, { "affs": [ 12 ], "name": "Weili Liu" }, { "affs": [ 0 ], "name": "Haifeng Liu" } ], "bibtex": "https://research.draconitic.com/paper/f8xg7nd739z3p.bib", "cited_by": 0, "doi": "10.34133/cancomm.0068", "fulltext_url": "https://europepmc.org/articles/PMC13748627", "id": "f8xg7nd739z3p", "issns": [ "2523-3548" ], "landing_url": "https://europepmc.org/article/MED/43011476", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Original Article" ], [ "openalex", "2740|Lung Cancer Treatments and Mutations" ] ], "openalex": "W7223023836", "pdf_url": "https://europepmc.org/articles/PMC13748627?pdf=render", "pmcid": "PMC13748627", "pmid": "43011476", "published": "2026-11-10", "publisher": "AAAS Science Partner Journal Program", "ris": "https://research.draconitic.com/paper/f8xg7nd739z3p.ris", "sources": [ { "first_seen": "2026-11-12T15:23:59Z", "native_id": "MED:43011476", "source": "europepmc", "url": "https://europepmc.org/article/MED/43011476" }, { "first_seen": "2026-11-13T12:26:35Z", "native_id": "PMC13748627", "source": "pmc", "url": "https://doi.org/10.34133/cancomm.0068" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2740|Lung Cancer Treatments and Mutations", "subfield": "general" } ], "title": "Dirozalkib versus Crizotinib in Advanced Anaplastic Lymphoma Kinase Inhibitor-Naïve ALK-Positive Non-Small-Cell Lung Cancer: A Multicenter, Randomized Phase III Trial.", "title_text": "Dirozalkib versus Crizotinib in Advanced Anaplastic Lymphoma Kinase Inhibitor-Naïve ALK-Positive Non-Small-Cell Lung Cancer: A Multicenter, Randomized Phase III Trial.", "type": "peer-reviewed", "updated_at": "2026-11-14T03:20:07Z", "url": "https://research.draconitic.com/paper/f8xg7nd739z3p", "venue": "Cancer communications (London, England)", "versions": [] }