Results from a dose-escalation/dose-expansion phase 1 trial of zanidatamab, a bispecific antibody against two domains of HER2, were recently published in the Lancet oncology. It was found to be effective in patients with locally advanced or metastatic solid tumors with amplification or overexpression of HER2.

Dose escalation phase

During the dose escalation phase, 46 patients were given zanidatumab at doses ranging from 5 mg/kg to 30 mg/kg every 1, 2, or 3 weeks, with no serious dose-limiting adverse events at the maximum tolerated dose. Based on these results, the recommended dose was 20 mg/kg every 2 weeks. Common treatment-related adverse events included diarrhea (52%), infusion-related adverse events (43%), and diarrhea (20%), all of which were identified as grade 1 or 2.

Dose escalation phase

In the dose expansion phase, zanidatumab was administered in a total of 86 cancer patients (22 biliary tract cancers, 28 colorectal cancers, and 36 other cancers), excluding breast and gastroesophageal cancers, for further study at the recommended dose. Of the 86 treated patients, a partial response or better was confirmed in 31 (37%) (38% in biliary tract cancer patients, 38% in colorectal cancer patients, and 36% in other cancers). Stable lesions were observed in 37% of all patients (24% of biliary tract cancers, 38% of colorectal cancers, and 44% of other cancers). In patients who responded, the median duration of response was found to be 6.9 months (8.5 months for biliary tract cancer, 5.6 months for colorectal cancer, and 9.7 months for other cancers). The median progression-free survival for all patients was observed to be 5.4 months (3.5 months for biliary tract cancer, 6.8 months for colorectal cancer, and 5.5 months for other cancers).

The researchers concluded that the results of this study demonstrated that zanitumumab was effective in patients with solid tumors with amplification or overexpression of HER2, including biliary tract and colorectal cancers. A number of studies are currently validating the effectiveness of zanitumumab.