Dirozalkib versus Crizotinib in Advanced Anaplastic Lymphoma Kinase Inhibitor-Naïve ALK-Positive Non-Small-Cell Lung Cancer: A Multicenter, Randomized Phase III Trial.
13 affiliations
- 1Department of Oncology, Jilin Provincial Cancer Hospital, Changchun, Jilin, P. R. China.
- 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, P. R. China.
- 3Department of Thoracic Medical Oncology, The Affiliated Cancer Hospital of Harbin Medical University, Harbin, Heilongjiang, P. R. China.
- 4Department of Thoracic Medical Oncology, Hunan Provincial Cancer Hospital, Changsha, Hunan, P. R. China.
- 5Department of Medical Oncology, Yunnan Provincial Cancer Hospital, Kunming, Yunnan, P. R. China.
- 6Department of Respiratory and Critical Care Medicine, Nanfang Hospital Affiliated to Southern Medical University, Guangzhou, Guangdong, P. R. China.
- 7Department of Thoracic Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, P. R. China.
- 8Department of Respiratory Oncology, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi, P. R. China.
- 9Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P. R. China.
- 10Department of Respiratory Medical Oncology, The Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China.
- 11Department of Oncology, The Affiliated Hospital of Chengde Medical University, Chengde, Hebei, P. R. China.
- 12Department of Medical Oncology, Meizhou People's Hospital, Meizhou, Guangdong, P. R. China.
- 13Department of Clinical Science, Xuanzhu Biopharmaceutical Co. Ltd., Beijing, P. R. China.
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).
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BibTeX
@article{liu2026dirozalkib,
title = {{Dirozalkib versus Crizotinib in Advanced Anaplastic Lymphoma Kinase Inhibitor-Naïve ALK-Positive Non-Small-Cell Lung Cancer: A Multicenter, Randomized Phase III Trial.}},
author = {Ying Liu and Xiangjiao Meng and Yan Yu and Jianhua Chen and Runxiang Yang and Laiyu Liu and Yanqiu Zhao and Ruifen Tian and Dianming Li and Ruiling Ning and Qingshan Li and Guowu Wu and Li Wang and Xianghui Duan and Xuejie Guo and Yan Hu and Weili Liu and Haifeng Liu},
journal = {Cancer communications (London, England)},
year = {2026},
month = nov,
doi = {10.34133/cancomm.0068},
url = {https://europepmc.org/article/MED/43011476},
note = {CC BY},
}
RIS
TY - JOUR
TI - Dirozalkib versus Crizotinib in Advanced Anaplastic Lymphoma Kinase Inhibitor-Naïve ALK-Positive Non-Small-Cell Lung Cancer: A Multicenter, Randomized Phase III Trial.
AU - Ying Liu
AU - Xiangjiao Meng
AU - Yan Yu
AU - Jianhua Chen
AU - Runxiang Yang
AU - Laiyu Liu
AU - Yanqiu Zhao
AU - Ruifen Tian
AU - Dianming Li
AU - Ruiling Ning
AU - Qingshan Li
AU - Guowu Wu
AU - Li Wang
AU - Xianghui Duan
AU - Xuejie Guo
AU - Yan Hu
AU - Weili Liu
AU - Haifeng Liu
PY - 2026
DA - 2026/11/10
JO - Cancer communications (London, England)
DO - 10.34133/cancomm.0068
UR - https://europepmc.org/article/MED/43011476
AB - 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).
SN - 2523-3548
ER -