Jazz Pharmaceuticals announced that the European Commission (EC) has granted conditional marketing authorisation for zanidatamab, a dual human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody, as monotherapy for the treatment of adults with unresectable locally advanced or metastatic HER2-positive (IHC 3+)[1] biliary tract cancer (BTC) previously treated with at least one prior line of systemic therapy.

BTCs, which include gallbladder cancer (GBC) and cholangiocarcinoma (CCA), are a rare and aggressive group of cancers, with most cases diagnosed at an advanced stage when curative surgery is no longer an option. Globally, approximately 26% of patients with BTC are HER2-positive, a biomarker associated with poorer outcomes compared to HER2-negative disease.

Zanidatamab is the first HER2-targeted therapy given conditional authorisation for HER2-positive BTC in the European Union (EU). Continued approval for this indication is contingent upon verification and description of clinical benefit in the ongoing Phase 3 HERIZON-BTC-302 trial, which is evaluating zanidatamab in combination with standard-of-care therapy versus standard-of-care therapy alone in the first-line setting for patients with HER2-positive BTC.

“People with HER2-positive biliary tract cancer who progress after first-line therapy face a challenging prognosis, with limited treatment options, poor tolerability, and median overall survival of only six to nine months,” said Arndt Vogel, MD, managing senior consultant and professor in the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School, Germany. “Zanidatamab provides a much-needed targeted monotherapy for this population, and in the HERIZON-BTC-01 trial, it demonstrated clinically meaningful and durable responses with a manageable safety profile. These data represent a welcome advance for patients with historically poor outcomes and highlight the importance of HER2 testing in biliary tract cancer to ensure eligible patients are identified for biomarker-driven treatment.”

The EC decision is based on data from the Phase 2b HERIZON-BTC-01 trial, which evaluated Ziihera in patients with previously treated, unresectable, locally advanced or metastatic HER2-positive BTC. This is the largest Phase 2b trial conducted to date specifically in this population. The study enrolled 87 patients, including 80 in Cohort 1 with centrally confirmed HER2-positive tumors (IHC 2+/ISH+ [n=18] or IHC 3+/ISH+ [n=62]). The trial achieved its primary endpoint of confirmed objective response rate (cORR) in Cohort 1, as assessed by independent central review (ICR). At a median follow-up of 21.9 months, zanidatamab demonstrated a cORR of 41.3% (95% CI: 30.4, 52.8), including two complete responses.11 The median duration of response (DOR) was 14.9 months (95% CI: (7.4, not reached), and the median overall survival (OS) was 15.5 months (95% CI: 10.4, 18.5).

Findings from a pre-specified subgroup analysis in patients with IHC 3+ tumours (n=62) showed that Ziihera demonstrated a cORR of 51.6% (95% CI: 38.6, 64.5), with a median DOR of 14.9 months (95% CI: 7.4, 24.0).2 The median OS in this subgroup was 18.1 months (95% CI: 12.2, 22.9).

The recommended dose of Ziihera is 20 mg/kg, administered as an intravenous infusion every two weeks until disease progression or unacceptable toxicity.

The safety profile for zanidatamab was evaluated in 87 patients with HER2-positive BTC (Cohorts 1 and 2) in HERIZON-BTC-01. The most common adverse reactions in this population were diarrhea (46%), infusion-related reaction (33.3%), abdominal pain (26.4%), anemia (25.3%) and fatigue (24.1%). Serious adverse reactions occurred in 16.1% of patients. The most frequent serious adverse reactions were diarrhea (2.3%), fatigue (2.3%), and increased alanine aminotransferase (2.3%).

“This conditional approval represents significant progress for the patients we serve who have been diagnosed with advanced HER2-positive BTC,” said Robert Iannone, MD., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. “Ziihera is the first HER2-targeted therapy authorised in the European Union specifically for this population, and the European Commission’s decision reflects both the strength of the HERIZON-BTC-01 data and the urgency for innovation in rare gastrointestinal cancers. This milestone reinforces our commitment to advancing biomarker-driven therapies that address serious unmet needs and improve patient outcomes. We are actively recruiting for our global Phase 3 trial in first-line HER2-positive BTC and continue to explore zanidatamab’s potential in other HER2-expressing tumours.”

“Biliary tract cancers are becoming more common worldwide and are increasingly affecting people under the age of 60, resulting in a significant social and economic burden,” said Zorana Maravic, chief executive officer at Digestive Cancers Europe (DiCE). “These cancers are typically diagnosed late, when patients have limited treatment options available and, unfortunately, their disease often progresses. Ziihera provides a much-needed alternative to chemotherapy for patients with HER2-positive BTC at this stage. It also brings hope to the digestive cancer patient community as another step in expanding the availability of targeted therapies.”

The European Commission authorisation extends to all European Union Member States, as well as Iceland, Norway, and Liechtenstein.

Source: Jazz Pharmaceuticals plc