As zanidatamab awaits an FDA approval decision, Jazz Pharmaceuticals is sharing long-term phase 2b data in advanced biliary tract cancer (BTC) for the HER2-targeted bispecific antibody.
The data set includes the first overall survival (OS) findings from the study, with zanidatamab demonstrating a median OS of 15.5 months compared to the typical six-month to nine-month prognosis for patients receiving chemotherapy after first-line therapy.
The results build on past data shared at last year’s American Society of Clinical Oncology (ASCO) annual meeting, confirming the 41.3% objective response rate (ORR)—the primary endpoint of the study—led to longer-term benefit.
“These results are really unprecedented,” Rob Iannone, M.D., global head of R&D at Jazz, told Fierce Biotech at this year’s ASCO meeting. “Compared to any other data with HER2 agents, it's just far superior.”
Previously, in a study of Roche's two anti-HER2 regimens, Herceptin and Perjeta, patients with metastatic BTC and HER2 overexpression experienced an ORR of 23% at an eight-month follow-up.
Jazz’s new data—shared Saturday at ASCO—were taken from a data cut of 87 patients receiving 20 mg/kg of zanidatamab intravenously once every two weeks. Patients who had previous HER2-targeted treatment were excluded from the trial.
Median duration of response, one of the study’s secondary endpoints, increased by about two months to 14.9 months, compared to the 12.4 months reported during a previous data cut.
“We were quite pleasantly surprised that that median actually increased in duration,” Iannone said. “That’s a considerable increase in median.”
When examining median OS by specific patient populations, zanidatamab demonstrated a higher OS of 18.1 months for 80 patients with IHC 3+ tumors and a lower 5.2 months for seven patients with IHC 2+ tumors.
One more patient also experienced a complete response since last year’s data cut, bringing the total complete response rate to 2.5% with two total patients.
Zanidatamab’s safety profile remained manageable, according to Jazz, with two (2.3%) patients discontinuing treatment due to treatment-related adverse events (TRAEs) and serious TRAEs reported in eight (9.2%) patients.
The new findings were included in the FDA application Jazz submitted for the Zymeworks-partnered prospect in April. Earlier this week, the FDA granted zanidatamab priority review for the treatment of previously treated, unresectable, locally advanced or metastatic HER2-positive BTC, with a decision expected by Nov. 29. If approved, the bispecific antibody would be the first HER2-targeted treatment specifically for the indication.
Jazz is currently running a global phase 3 trial of zanidatamab in combo with standard-of-care therapy in the first-line setting for HER2-positive BTC, with top-line data expected in 2028. The trial includes both IHC3+ and IHC2+ tumors.
Zanidatamab is a bispecific antibody designed to bind to two non-overlapping HER2 domains and cross-link neighboring HER2 proteins. Jazz in-licensed the asset from Zymeworks and is assessing the candidate in multiple solid tumor trials.
In January, the company posted top-line results in metastatic gastroesophageal cancer that found 84% of patients were kept alive for at least 18 months when receiving zanidatamab and chemotherapy.