Zymeworks announces updated clinical data for novel bispecific antibody, ZW25

Zymeworks Inc., announced the plenary presentation of updated ZW25 clinical data by Murali Beeram, a clinical investigator at the START Center for Cancer Care in San Antonio.

The data were presented at the Symposium on Molecular Targets and Cancer Therapeutics, sponsored by the European Organization for Research and Treatment of Cancer, NCI, and the American Association for Cancer Research. The title is “Single Agent Activity of ZW25, a HER2-Targeted Bispecific Antibody, in HER2-Expressing Gastroesophageal and Other Cancers.”

Data from Zymeworks’ ongoing multi-center phase I study showed single agent ZW25, a bispecific antibody, induced anti-tumor activity and was well tolerated in heavily pretreated patients with a variety of HER2-expressing cancers.

The plenary presentation includes all 24 gastroesophageal and other cancer patients treated at the phase II recommended dose, of which 17 were response-evaluable (defined as having measurable disease and at least one tumor restaging) at the time of data cut-off.

Of these 17 patients, eight had gastroesophageal cancers, four had colorectal cancer, and five had other HER2-expressing cancers including gallbladder, cholangiocarcinoma, cervical, fallopian tube and salivary gland. The participants in the study were heavily pretreated with a median of three prior cancer treatments.

The overall disease control rate, which includes patients with partial responses and stable disease was 82 percent. There were seven partial responses (41%), seven stable disease (41%) and three progressive disease (18%). The median progression-free survival in all 24 patients was 6.21 months (95% CI 1.94-9.33).

In the eight gastroesophageal cancer patients, who had a median of four prior systemic treatments, the response rate was 50 percent.

In the four colorectal and five other HER2-expressing cancer patients the response rate was 33 percent. Anti-tumor activity was assessed per RECIST every eight weeks.

In the study, ZW25 was well tolerated. All treatment-related adverse events were grade I or II with the exception of one patient with grade III fatigue, and no treatment-related serious adverse events were seen.

There were no grade IV or V adverse events. The most common adverse events (25% or greater) were diarrhea, infusion reaction and nausea.

“The favorable tolerability we have seen with ZW25 supports its use as both a single agent and in combination with approved anti-cancer agents,” said Diana Hausman, Zymeworks’ chief medical officer. “We are excited to be advancing ZW25’s development and have plans to explore its efficacy in a number of tumor types, including gastroesophageal and breast cancer.”

Enrollment in the first portion of the study (the dose-escalation phase) has been completed. The recommended single-agent dose was determined to be 20 mg/kg once every two weeks or 10 mg/kg weekly.

In the second part of the study (the cohort expansion phase), additional patients are being enrolled to further assess ZW25’s single-agent tolerability and anti-tumor activity against a variety of cancer types in different settings.

The third part of the study (the combination phase) is underway and is evaluating ZW25 in combination with selected chemotherapy agents in gastroesophageal and breast cancer patients with HER2 high or lower HER2 expression levels.

ZW25 is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding.

This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function and has led to encouraging anti-tumor activity in patients.

Zymeworks is developing ZW25 as a HER2-targeted treatment option for patients with any solid tumor that expresses HER2. FDA has granted Orphan Drug Designation to ZW25 for the treatment of both gastric and ovarian cancers.