In a Chinese phase II trial (HORIZON-Lung) reported in The Lancet Oncology, Li et al found that trastuzumab rezetecan, a novel antibody-drug conjugate, showed activity in patients with advanced HER2-positive non–small cell lung cancer (NSCLC).
Trastuzumab rezetecan consists of a HER2-directed antibody and DNA topoisomerase I inhibitor joined by a cleavable tetrapeptide-based linker.
Study Details
In the multicenter trial, 94 patients enrolled between April 2023 and December 2023 received trastuzumab rezetecan at 4.8 mg/kg every 3 weeks. Patients had to have locally advanced or metastatic NSCLC with an activating HER2 mutation and disease progression after or intolerance to platinum-based chemotherapy and anti–PD-1 treatment or anti–PD-L1 treatment. The primary endpoint was objective response rate on independent review committee assessment.
Key Findings
At data cutoff (in June 2024), the median duration of follow-up was 8.7 months (interquartile range = 7.0–10.4 months). Objective responses (all partial) were observed in 69 of 94 patients (73%, 95% confidence interval [CI] = 63.3%–82.0%). The median duration of response was not reached (95% CI = 8.3 months to not reached); 83.9% of responses were ongoing at 6 months, and 74% were ongoing at data cutoff. An additional 25% patients had stable disease, yielding a disease control rate of 98.9%.
Median progression-free survival was 11.5 months (95% CI = 9.9 months to not reached), with a 6-month rate of 86.8%.
Grade ≥ 3 treatment-related adverse events occurred in 62% of patients, most commonly decreased neutrophil count (40%), decreased white blood cell count (27%), anemia (23%), decreased platelet count (11%), and decreased lymphocyte count (7%). Treatment-related serious adverse events occurred in 23% of patients. Treatment-related adverse events led to treatment discontinuation in one patient. No treatment-related deaths were reported.
The investigators concluded: “Trastuzumab rezetecan showed clinically meaningful activity and manageable safety in patients with previously treated HER2-mutant NSCLC. Further trials are justified.”
Shun Lu, MD, of Shanghai Lung Cancer Center, Shanghai Jiao Tong University School of Medicine, Shanghai, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Jiangsu Hengrui Pharmaceuticals and others. For full disclosures of the study authors, visit thelancet.com.
