Cecilia Brown

Lung Cancers Today

Trastuzumab rezetecan showed “clinically meaningful activity” in patients who had received previous treatment for HER2-mutated non–small cell lung cancer (NSCLC), according to recent findings from the phase 2 HORIZON-Lung trial.
Ziming Li, MD, of the Shanghai Lung Cancer Center, the Shanghai Chest Hospital, and Shanghai Jiao Tong University School of Medicine, and colleagues conducted the study and published their findings in The Lancet Oncology.
The novel antibody–drug conjugate, also known as SHR-A1811, consists of a humanized HER2-directed monoclonal antibody, a cleavable tetrapeptide-based linker, and a DNA topoisomerase I inhibitor. Trastuzumab rezetecan previously showed “preliminary anti-tumour activity and a favourable safety profile” when evaluated in patients with HER2-mutated NSCLC in the phase 1 portion of the phase 1/2 study. Dr. Li and colleagues reported phase 2 results from the study in a recent publication in The Lancet Oncology, with a focus on a further evaluation of safety and efficacy at the recommended dose of trastuzumab rezetecan. The primary end point was the objective response rate as assessed by an independent review committee, in patients who received at least 1 cycle of study treatment. All patients who received at least 1 cycle of the study treatment were included in the safety analysis.
The multicenter, single-arm trial was conducted at 35 hospitals in China. The trial included 94 patients aged 18 to 75 years who had locally advanced or metastatic NSCLC with an activating HER2 mutation. All patients had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, as well as intolerance to or disease progression after platinum-based chemotherapy and anti–PD-1 or anti–PD-L1 treatment. More than half of patients (55%) were female and nearly all (98%) were Han Chinese. The patients received IV trastuzumab rezetecan 4.8 mg/kg once every 3 weeks.
The study investigators found that 73% of patients (95% CI, 63.3%-82.0%) had a confirmed objective response at a median follow-up of 8.7 months. The most common grade 3-4 treatment-related adverse events were decreased neutrophil count, occurring in 40% of patients; decreased white blood cell count, occurring in 27%; anemia, occurring in 23%; decreased platelet count, occurring in 11%; and decreased lymphocyte count, occurring in 7%.
The researchers reported that treatment-related serious adverse events occurred in 23% of patients. These treatment-related serious adverse events included decreased platelet count, occurring in 6%; decreased neutrophil count, also occurring in 6%; interstitial lung disease, occurring in 5%; decreased white blood cell count, occurring in 4%; anemia, occurring in 4%; vomiting, occurring in 3%; pneumonia, occurring in 3%; and hyponatremia, occurring in 2%. Occurring in 1% were pyrexia, small intestinal obstruction, nausea, and chronic obstructive pulmonary disease. No treatment-related deaths were reported.
Based on these findings, Dr. Li and colleagues concluded that trastuzumab rezetecan “showed clinically meaningful activity and manageable safety in patients with previously treated HER2-mutant NSCLC” and that “further trials are justified.”
Reference
Li Z, Wang Y, Sun Y, et al. Trastuzumab rezetecan, a HER2-directed antibody–drug conjugate, in patients with advanced HER2-mutant non-small-cell lung cancer (HORIZON-Lung): phase 2 results from a multicentre, single-arm study.  Lancet Oncol. Published online February 2025. doi:https://doi.org/10.1016/s1470-2045(25)00012-9

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Trastuzumab rezetecan showed “clinically meaningful activity” in patients who had received previous treatment for HER2-mutated non–small cell lung cancer (NSCLC).