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Dirozalkib versus Crizotinib in Advanced Anaplastic Lymphoma Kinase Inhibitor-Naïve ALK -Positive Non-Small-Cell Lung Cancer: A Multicenter, Randomized Phase III Trial

Year: 2026

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

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).

Source: 癌症：英文版

DOI: 10.34133/cancomm.0068