Zanidatamab Elicits Responses in Previously Treated HER2-Amplified Biliary Tract Cancers

Neil Josephson, MD

Zanidatamab monotherapy produced responses in previously treated patients with HER2-amplified and -expressing biliary tract cancers, according to topline data from the phase 2b HERIZON-BTC-01 trial (NCT04466891).¹

Patients treated with the bispecific antibody achieved a confirmed objective response rate (ORR) of 41.3% (95% CI, 30.4%-52.8%), per independent central review (ICR). Additionally, the median duration of response (DOR) was 12.9 months (95% CI, 5.95–not reached).

“Through our work with the biliary tract cancers community, we see first-hand the challenge these patients face in not only getting a diagnosis, but in the limited treatment options available,” Stacie Lindsey, founder and chief executive officer of the Cholangiocarcinoma Foundation, stated in a press release. “Each investigative trial begins to close the gap on this high unmet medical need by helping to bring more treatment options to patients [with biliary tract cancers], and we’re looking forward to watching zanidatamab’s progression through the global regulatory review process.”

The global, multicenter, open-label, single-arm HERIZON-BTC-01 study evaluated zanidatamab monotherapy in previously treated patients with HER2 amplification, as determined centrally by in situ hybridization (ISH) in tumor tissue. Patients with tumor tissue showing HER2 immunohistochemistry (IHC) 2+ or 3+ staining were enrolled into cohort 1, the primary efficacy cohort. Cohort 2 included patients with tumor tissue showing HER2 IHC 0 or 1+ staining.

All patients were required to be at least 18 years of age and have histologically or cytologically confirmed biliary tract cancer—including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer—that was locally advanced or metastatic and not eligible for curative resection, transplantation, or ablative therapies.² Other key inclusion criteria included at least 1 prior gemcitabine-containing systemic chemotherapy regimen for advanced disease; disease progression after or intolerance to the most recent prior therapy; a positive test for HER2 amplification by ISH assay at a central laboratory on a new biopsy or archival tissue; an ECOG performance status of 0 or 1; and adequate organ function.

Patients who received systemic anticancer therapy within 3 weeks of the first dose of zanidatamab, received radiotherapy within 2 weeks of the first dose of zanidatamab, had prior treatment with HER2-targeted agents, had untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks of start of study treatment, or known leptomeningeal disease were excluded from the trial.

ICR-assessed ORR per RECIST v1.1 criteria served as the trial’s primary end point. Secondary end points included DOR, the proportion of patients with a DOR of at least 16 weeks, disease control rate, progression-free survival, overall survival, and safety.

Regarding safety, findings from the trial were consistent with previously reported data for zanidatamab monotherapy in other studies, and no new safety signals were identified.

Full results from HERIZON-BTC-01 are expected to be presented at a medical meeting in 2023.

“We are thrilled to report these positive topline data from the HERIZON-BTC-01 clinical trial, which further support the potential of zanidatamab as a new chemotherapy-free therapeutic option for HER2-amplified and expressing BTC. These data demonstrate that zanidatamab, as a single agent, improves on the current standard of care for patients in a difficult-to-treat disease who currently have a poor prognosis based on the limited treatment options currently available,” said Neil Josephson, MD, chief medical officer at Zymeworks. “I want to thank all of the patients, their families and the investigators who participated in this important study.”

References

1. Zymeworks announces positive topline data in the pivotal HERIZON-BTC-01 trial of zanidatamab. News release. Zymeworks Inc. December 19, 2022. Accessed December 20, 2022. https://bit.ly/3PFJUdc
2. A study of ZW25 (zanidatamab) in subjects with advanced or metastatic HER2-amplified biliary tract cancers (HERIZON-BTC-01). ClinicalTrials.gov. Updated September 16, 2022. Accessed December 20, 2022. https://clinicaltrials.gov/ct2/show/NCT04466891?term=NCT04466891&draw=2&rank=1