Trastuzumab Rezetecan for Patients With HER2-Mutated Non-Small Cell Lung Cancer
According to results from the phase 2 HORIZON-Lung trial, trastuzumab rezetecan, a novel human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate, demonstrated promise among patients with HER2-mutated non-small cell lung cancer (NSCLC).
“In the phase 1 portion of this phase 1/2 study, trastuzumab rezetecan showed preliminary anti-tumour activity and a favourable safety profile in patients with HER2-mutant [NSCLC],” stated Ziming Li, MD, Shanghai Chest Hospital, Shanghai, China, and coauthors. Here, researchers “aimed to further evaluate the activity and safety of trastuzumab rezetecan at the recommended dose.”
In this multicenter, single-arm study, 94 patients with HER2-mutated locally advanced or metastatic NSCLC who were either intolerant to or experienced disease progression after platinum-based chemotherapy and anti-PD-(L)1 treatment were assigned to receive 4.8 mg/kg of trastuzumab rezetcan once every 3 weeks. The primary end point was objective response rate (ORR) via an independent review committee. A key secondary end point was safety.
At a median follow up of 8.7 months, the ORR was 73%. The most common grade 3/4 treatment-related adverse events included decreased neutrophil count (40%), decreased white blood cell count (27%), anemia (23%), decreased platelet count (11%), and decreased lymphocyte count (7%). Serious treatment-related adverse events occurred in 23% of patients and most frequently included decreased platelet count (6%), decreased neutrophil count (6%), interstitial lung disease (5%), decreased white blood cell count (4%), anemia (4%), vomiting (3%), pneumonia (3%), hyponatremia (2%), pyrexia (1%), small intestinal obstruction (1%), nausea (1%), and chronic obstructive pulmonary disease (1%). No treatment-related deaths occurred.
“Trastuzumab rezetecan showed clinically meaningful activity and manageable safety in patients with previously treated HER2-mutant NSCLC,” concluded Dr Li et al. “Further trials are justified.”
Source:
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 25, 2025. doi: 10.1016/S1470-2045(25)00012-9
