Safety and Efficacy of Zanidatamab in BTC

In an interview discussing the latest clinical data for zanidatamab in biliary tract cancer (BTC), Arndt Vogel, MD, Phd, professor and clinician scientist at the University of Toronto, highlights the compelling efficacy and manageable safety profile of the novel agent. Vogel points to the phase 2 trial (NCT04466838) as a significant step forward for a patient population with limited treatment options.

Vogel notes that this was one of the largest phase 2 studies in this population, including 87 patients with previously treated BTC. He underscores the impressive objective response rate (ORR) of 41%, which he contrasted sharply with the efficacy of standard-of-care second-line chemotherapy.

"If you compare to chemotherapy, where we typically see a second-line response rate in the single digits—around 7% to 8%—a response rate of 41% with zanidatamab is truly highlighting the efficacy of this targeted therapy in BTC." This robust response rate is a crucial indicator of the drug's potential to significantly impact patient outcomes.

Beyond the high response rate, the duration of response (DOR) was also a key highlight, with a median of 1 year. This suggests that patients who respond to zanidatamab can experience a sustained benefit, an important factor in managing advanced disease. Vogel also mentions a progression-free survival (PFS) of approximately 6 months, which he notes is in line with what is typically seen with effective targeted therapies.

"Overall, I think the data for patients in the second-line setting, for these pretreated patients, are really convincing and offer a meaningful improvement in outcomes for this group," he concluded.

Regarding safety, Vogel emphasizes that zanidatamab is "definitely manageable" and "very well tolerated by the majority of patients." He notes that common adverse events associated with HER2-directed therapies, such as diarrhea, were observed but were manageable. He points out that the safety profile is "clearly in favor of this drug," making it highly attractive for clinical use.

Vogel provides specific details on the severity of adverse events, noting, "When we look at grade 3 side effects, it's mainly diarrhea, with a rate of 5%." He adds that all other grade 3 adverse events were in the single digits, further reinforcing the drug's tolerability. Vogel concludes by expressing optimism about the drug's potential, noting that its favorable risk-benefit profile makes it an interesting and valuable addition to the therapeutic landscape for BTC.