Jiving with Jazz after $325M opt-in, Zymeworks links HER2 bispecific to 84% survival after 18 months

Fresh from its $325 million opt-in, Jazz Pharmaceuticals has posted phase 2 data on its HER2-targeted bispecific antibody zanidatamab. The Zymeworks-partnered prospect kept 84% of people with metastatic gastroesophageal cancer alive for at least 18 months when given in combination with chemotherapy.

Jazz took up its option on zanidatamab late last year after seeing top-line data from a pivotal clinical trial in previously treated HER2-amplified biliary tract cancers (BTCs). The BTC study is one of two late-phase zanidatamab programs. In parallel, Jazz and Zymeworks are running a pivotal zanidatamab clinical trial in metastatic gastroesophageal adenocarcinoma (mGEA) that is scheduled to deliver full data next year.

While working to wrap up the pivotal study, the partners have delivered the first overall survival (OS) data from a phase 2 GEA trial. The trial is testing zanidatamab in combination with chemotherapy in first-line metastatic, HER2-expressing GEA, a similar population to the pivotal study.

After 18 months, the OS rate in the 42 evaluable patients was 84%. The study is yet to reach the median OS after a median follow-up of 26.5 months. The objective response rate was 79%, with three patients having complete responses. The median duration of response was 20.4 months, and median progression-free survival was 12.5 months.

A bigger test for zanidatamab, namely the phase 3 readout, looms on the horizon. But the partners are happy with what they have seen so far, as Rob Iannone, M.D., global head of research and development of Jazz, said.

“We are very encouraged by the data from this phase 2 trial, which demonstrate zanidatamab administered with chemotherapy is a highly active treatment regimen and resulted in significant and durable tumor response in the first-line setting for patients with advanced HER2-expressing mGEA. These results showcase zanidatamab's potential as a foundational treatment for patients with HER2-positive mGEA,” Iannone said. 

The potential to treat GEA by targeting HER2 was confirmed in 2010 when researchers showed that adding Roche’s Herceptin to chemotherapy extended median overall survival from 11.1 months to 13.8 months. Jazz and Zymeworks are looking to clear that bar in a pivotal zanidatamab study that includes a Herceptin-plus-chemotherapy control arm.