Dirozalkib Phase III Trial Shows PFS Gain Over Crizotinib in ALK-Positive NSCLC

Xuanzhu Biopharmaceutical presented Phase III clinical data for dirozalkib in first-line ALK-positive advanced non-small cell lung cancer, showing improvements in progression-free survival, objective response rate, duration of response and intracranial efficacy versus crizotinib. Dirozalkib was approved by the NMPA in August 2025 for first-line treatment of ALK-positive locally advanced or metastatic NSCLC in patients who have not received prior ALK inhibitor therapy.

The DIAMOND-2 trial (NCT05204628) was a multicenter, randomized, open-label Phase III study conducted in China. A total of 275 patients with ALK-positive advanced NSCLC were enrolled and randomized 1:1 to receive either dirozalkib 500 mg once daily or crizotinib 250 mg twice daily.

Median progression-free survival for dirozalkib was 31.3 months, compared to 12.9 months for crizotinib. This translated to a 53% reduction in the risk of disease progression, with a hazard ratio of 0.47 and P < 0.0001.

Dirozalkib achieved an objective response rate of 88.5%. Median duration of response was 32.1 months, and disease control rate was 95.4%.

Among patients with measurable brain metastases at baseline, intracranial objective response rate was 91.7% for dirozalkib versus 11.1% for crizotinib. Dirozalkib significantly prolonged intracranial progression-free survival and reduced the risk of intracranial disease progression by 55%, with a hazard ratio of 0.45 and P = 0.0003.

Safety data showed a favorable profile, with primarily mild Grade 1–2 gastrointestinal adverse events. Only 1.5% of patients discontinued therapy due to drug-related adverse events.

Dirozalkib is a next-generation, oral ALK inhibitor. The source article said it demonstrates potent inhibition against resistance mutations including G1202R and I1171N, and shows strong penetration of the blood-brain barrier.