Zymeworks unveiled new phase 1 clinical data from its lead bispecific antibody, ZW25, demonstrating an overall response rate of just 36%, the result of 12 partial responses, as a single-agent treatment in a variety of heavily pretreated, HER2-expressing cancers.
With ZW25 as its flagship, the biotech inked a bispecific antibody development deal with Janssen late last year, involving as many as six products and worth up to $1.1 billion, including sales royalties. Zymeworks’ Azymetric platform forges antibodies able to bind to two different targets, spurring multiple effects while potentially reducing the chances of toxicity and drug resistance.
But in 18 breast cancer patients, who had received a median of six prior systemic regimens, the combined disease control rate—which included patients with partial drug responses or stable disease—was 50%. The DCR was 56% in nine gastroesophageal cancer patients, as well as four of six patients with other HER2+ cancers, including colorectal cancer.
However, 68% of overall patients, with measurable disease and at least one restaging scan, saw a decrease in their target lesions, giving the company a measure of confidence. In addition, ZW25 was well tolerated at all dose levels, with lower-grade adverse events and no discontinuations.
“To see this level of single-agent activity without any concomitant chemotherapy in these advanced heavily pretreated patients is encouraging,” said principal investigator Funda Meric-Bernstam, chair of the Department of Investigational Cancer Therapeutics at MD Anderson Cancer Center, who presented the 50-person study at the American Society of Clinical Oncology’s annual meeting in Chicago.
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“Given ZW25’s anti-tumor activity and safety profile, we are excited to expand the number of clinical trials we have underway for this program,” added Diana Hausman, Zymeworks’ chief medical officer. “We believe ZW25 could be used as monotherapy or readily combined with a number of approved anti-cancer treatments to further leverage its activity.”
The adaptive phase 1 study includes three parts, with first dose-escalation stage being completed. Additional patients are currently being enrolled in the expansion stage.
The third stage, which is also underway, is evaluating ZW25 in combinations with paclitaxel, capecitabine and vinorelbine chemotherapies, in gastroesophageal and breast cancer patients with varying HER2 expression levels.
The top future priority for ZW25 lies in HER2-high gastroesophageal cancer, which saw a 44% ORR as a single agent in late-stage disease, the company said. A potential phase 2/3 single-agent study is planned for the second half of 2019, pending discussions with the FDA.
Other HER2-high diseases—such as colorectal cancer, where a HER2-targeted agent has not yet been approved—will be studied as well.
In addition, new combination studies are planned to launch later this year. Zymeworks said it hopes to pair ZW25 with chemotherapies in earlier lines of treatment for HER2-high gastroesophageal and breast cancers, as well as in combinations with other anti-cancer agents in lower HER2-expressing cancers.
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The specific combinations have not been disclosed, however, Zymeworks has signed collaborations with several big pharma companies.
In 2016, Zymeworks signed another bispecific antibody discovery deal with GlaxoSmithKline, worth up to $908 million in commercial bonuses, should everything pay off. In the months prior, GSK agreed to a collaboration based on another Zymeworks platform, Efect, to develop antibodies that induce specific immune responses.
And before that, Zymeworks had signed additional deals with Merck, Celgene and Eli Lilly, totaling over $4 billion in possible spoils.
Its shares were however off premarket Monday morning, down nearly 4% on the neither great nor awful results.