Updated data from the phase 2b HERIZON-BTC-01 trial reveals that zanidatamab (ZW25) provides a durable clinical benefit for patients with pretreated, advanced, unresectable, or metastatic HER2-amplified biliary tract cancer (BTC). The study, presented at the 2024 American Society of Clinical Oncology Annual Meeting, highlights the potential of zanidatamab as a targeted therapy in this challenging cancer.
Efficacy of Zanidatamab
The confirmed objective response rate (cORR) with zanidatamab was 41.3%. The disease control rate (DCR) was 68.8%, consistent with the study's primary analysis. Notably, the median duration of response was 14.9 months (95% CI, 7.4-not reached), indicating a sustained benefit. The median overall survival (OS) in the cohort of patients with immunohistochemistry (IHC) 2+ or 3+ was 15.5 months (95% CI, 10.4-18.5). At 6 and 12 months, the OS rates were 80.3% (95% CI, 69.4%-87.6%) and 56.2% (95% CI, 44.3%-66.5%), respectively.
Safety Profile
The safety profile of zanidatamab remained consistent with previous reports. Most patients (96.6%) experienced treatment-emergent adverse effects (TEAEs), with 51.7% experiencing grade 1 or 2 treatment-related AEs (TRAEs) and 20.7% experiencing grade 3 or 4 TRAEs. Serious TRAEs were observed in 9.2% of patients. Common all-grade and grade 3 to 4 TRAEs included diarrhea (36.8%; 4.6%), infusion-related reactions (IRR; 33.3%; 1.1%), decreased ejection fraction (10.3%; 3.4%), nausea (9.2%; 1.1%), and increases in alanine transaminase (ALT; 6.9%; 1.1%) and aspartate aminotransferase (AST; 6.9%; 2.3%).
Expert Commentary
Shubham Pant, MD, MBBS, from The University of Texas MD Anderson Cancer Center, noted that zanidatamab is a bispecific anti-HER2 antibody that binds to two domains on HER2. In the HERIZON-BTC-01 trial, patients received zanidatamab intravenously every two weeks. Pant highlighted the significance of the 15.5-month overall survival in this pretreated patient population, emphasizing the importance of the duration of response. He also pointed out that zanidatamab, as a targeted therapy, is relatively well-tolerated, with manageable adverse effects.
Ongoing Research
A randomized, phase 3 trial is ongoing, evaluating zanidatamab in combination with standard-of-care therapy in the frontline setting for patients with HER2-positive biliary tract cancer.
