HER2-targeted therapy

The international, multicenter, single-arm, phase IIb HERIZON-BTC-01 trial (NCT04466891) enrolled 87 patients with HER2-amplified (by fluorescence in situ hybridization), unresectable, locally advanced or metastatic biliary tract cancer whose disease progressed on prior gemcitabine-based therapy. Cohort 1 included 80 patients with HER2 2+ or 3+ expression by immunohistochemistry (IHC), while cohort 2 included seven patients with HER2 0+ or 1+ expression by IHC. All patients received zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, at a dose of 20 mg/kg intravenously every 2 weeks. At a median follow-up of 12.4 months, the following results were observed:[22][Level of evidence C3]

The international, multicenter, single-arm, phase IIb HERIZON-BTC-01 trial (NCT04466891) enrolled 87 patients with HER2-amplified (by fluorescence in situ hybridization), unresectable, locally advanced or metastatic biliary tract cancer whose disease progressed on prior gemcitabine-based therapy. Cohort 1 included 80 patients with HER2 2+ or 3+ expression by immunohistochemistry (IHC), while cohort 2 included seven patients with HER2 0+ or 1+ expression by IHC. All patients received zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, at a dose of 20 mg/kg intravenously every 2 weeks. At a median follow-up of 12.4 months, the following results were observed:[22][Level of evidence C3]

In cohort 1, the objective response rate was 41.3% (95% CI, 30.4%–52.8%). The median duration of response was 12.9 months (95% CI, 6.0–not reached).

The international, multicenter, single-arm, phase IIb HERIZON-BTC-01 trial (NCT04466891) enrolled 87 patients with HER2-amplified (by fluorescence in situ hybridization), unresectable, locally advanced or metastatic biliary tract cancer whose disease progressed on prior gemcitabine-based therapy. Cohort 1 included 80 patients with HER2 2+ or 3+ expression by immunohistochemistry (IHC), while cohort 2 included seven patients with HER2 0+ or 1+ expression by IHC. All patients received zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, at a dose of 20 mg/kg intravenously every 2 weeks. At a median follow-up of 12.4 months, the following results were observed:[22][Level of evidence C3]

The median PFS was 5.5 months in cohort 1 (95% CI, 3.7–7.2) and 1.9 months (95% CI, 1.2–not estimable) in cohort 2.

The international, multicenter, single-arm, phase IIb HERIZON-BTC-01 trial (NCT04466891) enrolled 87 patients with HER2-amplified (by fluorescence in situ hybridization), unresectable, locally advanced or metastatic biliary tract cancer whose disease progressed on prior gemcitabine-based therapy. Cohort 1 included 80 patients with HER2 2+ or 3+ expression by immunohistochemistry (IHC), while cohort 2 included seven patients with HER2 0+ or 1+ expression by IHC. All patients received zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, at a dose of 20 mg/kg intravenously every 2 weeks. At a median follow-up of 12.4 months, the following results were observed:[22][Level of evidence C3]

Serious treatment-related adverse events occurred in 8% of patients. Zanidatamab was discontinued in two patients: one due to reduced ejection fraction and one due to pneumonitis. Diarrhea (37%) and infusion reactions with the first cycle (33%) were relatively common, but mostly low-grade.

The international, multicenter, single-arm, phase IIb HERIZON-BTC-01 trial (NCT04466891) enrolled 87 patients with HER2-amplified (by fluorescence in situ hybridization), unresectable, locally advanced or metastatic biliary tract cancer whose disease progressed on prior gemcitabine-based therapy. Cohort 1 included 80 patients with HER2 2+ or 3+ expression by immunohistochemistry (IHC), while cohort 2 included seven patients with HER2 0+ or 1+ expression by IHC. All patients received zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, at a dose of 20 mg/kg intravenously every 2 weeks. At a median follow-up of 12.4 months, the following results were observed:[22][Level of evidence C3]

The FDA has granted breakthrough therapy designation for zanidatamab in this setting, but it is not yet FDA approved.

The DESTINY-PanTumor02 trial (NCT04482309), reported in abstract form, was tumor-agnostic (enrolled patients with HER2-positive tumors from any site) but included a subset of 41 patients with biliary tract cancer.[23][Level of evidence C3]

The DESTINY-PanTumor02 trial (NCT04482309), reported in abstract form, was tumor-agnostic (enrolled patients with HER2-positive tumors from any site) but included a subset of 41 patients with biliary tract cancer.[23][Level of evidence C3]

The overall response rate was 22% in this subset of patients.

The phase II HERB trial (NCT04482309) enrolled 32 patients (24 with HER2-positive disease, 8 with HER2-low disease) with biliary tract cancers refractory to, or intolerant of, a gemcitabine-containing regimen. All patients received trastuzumab deruxtecan.[24][Level of evidence C3]

The phase II HERB trial (NCT04482309) enrolled 32 patients (24 with HER2-positive disease, 8 with HER2-low disease) with biliary tract cancers refractory to, or intolerant of, a gemcitabine-containing regimen. All patients received trastuzumab deruxtecan.[24][Level of evidence C3]

Among the patients with HER2-positive disease, the overall response rate was 36.4%. The median PFS was 5.1 months (95% CI, 3.0–7.3), and the median OS was 7.1 months (95% CI, 4.7–14.6).

The phase II HERB trial (NCT04482309) enrolled 32 patients (24 with HER2-positive disease, 8 with HER2-low disease) with biliary tract cancers refractory to, or intolerant of, a gemcitabine-containing regimen. All patients received trastuzumab deruxtecan.[24][Level of evidence C3]

Among the small sample of eight patients with HER2-low disease, the overall response rate was 12.5%. The median PFS was 3.5 months (95% CI, 1.2–5.5), and the median OS was 8.9 months (95% CI, 3.0–12.8).

The tumor-agnostic phase II SGNTUC-019 study (NCT04579380) evaluated the combination of tucatinib and trastuzumab. The trial included a cohort of 30 patients with previously treated HER2-overexpressing or HER2-amplified biliary tract cancer.[25][Level of evidence C3]

The tumor-agnostic phase II SGNTUC-019 study (NCT04579380) evaluated the combination of tucatinib and trastuzumab. The trial included a cohort of 30 patients with previously treated HER2-overexpressing or HER2-amplified biliary tract cancer.[25][Level of evidence C3]

At a median follow-up of 10.8 months, the objective response rate was 46.7% (90% CI, 30.8%–63.0%), with a disease control rate of 76.7% (90% CI, 60.6%–88.5%).

The tumor-agnostic phase II SGNTUC-019 study (NCT04579380) evaluated the combination of tucatinib and trastuzumab. The trial included a cohort of 30 patients with previously treated HER2-overexpressing or HER2-amplified biliary tract cancer.[25][Level of evidence C3]

The median PFS was 5.5 months (90% CI, 3.9–8.2).

The tumor-agnostic phase II SGNTUC-019 study (NCT04579380) evaluated the combination of tucatinib and trastuzumab. The trial included a cohort of 30 patients with previously treated HER2-overexpressing or HER2-amplified biliary tract cancer.[25][Level of evidence C3]

The most common treatment-related adverse events were pyrexia (43.3%) and diarrhea (40%). Adverse events caused no deaths but led one patient to discontinue treatment.