Results From the Phase 2b HERIZON-BTC-01 Study of Zanidatamab in Previously Treated HER2-Amplified BTC

Researchers present preliminary findings from the HERIZON-BTC-01 study, which investigated zanidatamab’s efficacy in patients with HER2-positive biliary tract cancer.

Research continues to focus on improving clinical outcomes of second-line treatments in patients with advanced biliary tract cancer (BTC), and researchers are investigating different therapeutic targets, such as HER2, a protein that encourages cell growth and accelerates the spread of cancers.^1-3 In patients with breast, lung, and gastric cancers, HER2-targeted therapies have shown clinical benefit, but there is no approved HER2-targeted therapy for patients with BTC at this time.² In a phase 1 trial, which included patients with BTC, zanidatamab demonstrated promising activity targeting HER2.⁴ HERIZON-BTC-01, a phase 2b study investigating the efficacy of zanidatamab in patients with HER2-positive BTC, was presented by Shubham Pant, MD, MBBS, at ASCO 2023.²

HERIZON-BTC-01 is a global, multicenter, single-arm, phase 2b trial of zanidatamab in patients with HER2-amplified, unresectable, locally advanced, or metastatic BTC following progression on previous gemcitabine-based therapy. In September 2020, this ongoing study launched and has since completed recruitment. Confirmed objective response rate (cORR) was the primary end point, and select secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.² A total of 87 patients were placed in either cohort 1 or cohort 2 depending on their immunohistochemistry (IHC) test score: 80 patients were placed in cohort 1 (IHC 2+ or 3+) and 7 patients in cohort 2 (IHC 0 or 1+). In cohort 1, 41 patients had gallbladder cancer, 23 patients had intrahepatic cholangiocarcinoma (CCA), and 16 patients had extrahepatic CCA. Results from cohort 2 were not included as it contained a small sample size and did not reveal any unique responses.²

In patients with treatment-refractory HER2-positive BTC, zanidatamab showed antitumor activity while exhibiting a manageable and tolerable safety profile.

The cORR of patients in cohort 1 was 41.3%, confirmed by both independent central review and investigator assessment.² In addition, in cohort 1, the DCR was 68.8%, and 68.4% of evaluable patients had a decrease in target lesions.² The median PFS was 5.5 months in cohort 1, and OS data are not yet available.² The median duration of treatment was 5.6 months, median DOR was 12.9 months, and median time to first response was 1.8 months.² The most common treatment-related adverse events (TRAEs) of any grade in both cohorts included diarrhea (n=36), infusion-related reactions (n=30), decrease in ejection fraction (n=11), nausea (n=9), and anemia (n=6).² Only 2 patients experienced TRAEs leading to treatment discontinuation (grade 2 decrease in ejection fraction and grade 3 pneumonitis).² No treatment-related deaths occurred.²

In patients with treatment-refractory HER2-positive BTC, zanidatamab showed antitumor activity while exhibiting a manageable and tolerable safety profile. In light of these preliminary results, Dr Pant concluded that zanidatamab may prove to be beneficial in patients with HER2-positive BTC.²

References

1. Valle JW, Kelley RK, Nervi B, Oh DY, Zhu AX. Biliary tract cancer. Lancet. 2021;397(10272):428-444.
2. Pant S, Fan J, Oh D-Y, et al. Results from the pivotal phase 2b HERIZON-BTC-01 study: zanidatamab in previously-treated HER2-amplified biliary tract cancer (BTC). Presented at: ASCO 2023 Annual Meeting, June 2-6, 2023; Chicago, IL.
3. Connell CM, Doherty GJ. Activating HER2 mutations as emerging targets in multiple solid cancers. ESMO Open. 2017;2(5):e000279.
4. Meric-Bernstam F, Beeram M, Hamilton E, et al. Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study. Lancet Oncol. 2022;23(12):1558-1570.