Jazz Shares Groundbreaking HER2 Biliary Tract Cancer Data Before FDA Decision

Jazz Pharmaceuticals has revealed promising phase 2b data for zanidatamab, a HER2-targeted bispecific antibody, in the treatment of advanced biliary tract cancer (BTC). This follows the company's submission of an FDA application for zanidatamab in April. As the FDA deliberates on its approval, Jazz is presenting long-term survival data that could significantly impact BTC treatment paradigms.

The recent data includes the first overall survival (OS) findings, showing a median OS of 15.5 months for zanidatamab-treated patients. This is a notable improvement over the typical six to nine months OS for patients undergoing chemotherapy after first-line therapy. Last year's American Society of Clinical Oncology (ASCO) annual meeting had already highlighted the antibody’s 41.3% objective response rate (ORR), the study's primary endpoint, which has now translated into longer-term benefits.

Rob Iannone, M.D., global head of R&D at Jazz Pharmaceuticals, emphasized the unprecedented nature of these results, particularly when compared to other HER2-targeting agents. For instance, a study of Roche's Herceptin and Perjeta in metastatic BTC patients with HER2 overexpression showed an ORR of just 23% at eight months.

The phase 2b trial involved 87 patients who received 20 mg/kg of zanidatamab intravenously every two weeks. Notably, patients with prior HER2-targeted treatments were excluded. The median duration of response, a secondary endpoint, increased to 14.9 months from the earlier reported 12.4 months. Iannone expressed pleasant surprise at this increase, noting it as a considerable improvement.

Further analysis revealed that zanidatamab provided varied benefits across different patient subgroups. For 80 patients with IHC 3+ tumors, the median OS was 18.1 months, whereas it was only 5.2 months for seven patients with IHC 2+ tumors. Additionally, the complete response rate rose to 2.5%, with one more patient achieving a complete response since last year.

Zanidatamab also maintained a manageable safety profile. Only 2.3% of patients discontinued treatment due to treatment-related adverse events (TRAEs). Serious TRAEs were reported in 9.2% of patients. These new findings were part of the FDA application submitted by Jazz Pharmaceuticals in April. The FDA has since granted zanidatamab priority review for previously treated, unresectable, locally advanced, or metastatic HER2-positive BTC, with a decision expected by November 29. If approved, this would mark the first HER2-targeted treatment specifically for this condition.

Jazz is also conducting a global phase 3 trial of zanidatamab in combination with standard-of-care therapy as a first-line treatment for HER2-positive BTC, with top-line results anticipated in 2028. This trial includes both IHC 3+ and IHC 2+ tumors.

Zanidatamab is engineered to bind to two distinct HER2 domains and cross-link neighboring HER2 proteins. Jazz Pharmaceuticals in-licensed this asset from Zymeworks and is evaluating it across various solid tumor trials. Earlier in January, Jazz announced promising top-line results from a metastatic gastroesophageal cancer study, where 84% of patients survived at least 18 months when treated with zanidatamab and chemotherapy.