Findings from a new phase 1 study suggest the novel HER2-targeting antibody-drug conjugate trastuzumab duocarmazine is safe and effective in patients with advanced solid tumours.
The research included a dose-escalation cohort comprising 39 adults with locally advanced or metastatic solid tumours with variable HER2 status who were refractory to standard cancer treatment. A separate cohort of 146 patients with breast, gastric, urothelial or endometrial cancer were enrolled in the dose-expansion phase.
One dose-limiting toxic effect (pneumonitis) occurred at the highest dose (2.4 mg/kg) of trastuzumab duocarmazine in the dose-escalation phase. Grade 3-4 treatment-related adverse events (TRAEs) reported more than once in the dose-escalation phase were keratitis (n=3) and fatigue (n=2). Based on all available data, the recommended phase 2 dose was set at 1.2 mg/kg.
In the dose-expansion phase, TRAEs were reported by 11 per cent and were most commonly infusion-related reactions (1%) and dyspnoea (1%). Most patients (71%) had ≥1 ocular adverse event, with grade 3 events reported in 7 per cent. No patients died from TRAEs. Four patients died due to disease progression.
In the breast cancer dose-expansion cohorts, 33 per cent of assessable patients with HER2-positive breast cancer achieved an objective response (all partial responses). Partial responses were also observed in one (6%) of 16 patients with gastric cancer, four (25%) of 16 with urothelial cancer and five (39%) of 13 with endometrial cancer.
The authors concluded that trastuzumab duocarmazine “shows notable clinical activity in heavily pretreated patients with HER2-expressing metastatic cancer, including HER2-positive trastuzumab emtansine-resistant and HER2-low breast cancer”.
Further investigation of trastuzumab duocarmazine for HER2-positive breast cancer is ongoing, and trials for HER2-low breast cancer and other HER2-expressing cancers are in preparation.
