Zymeworks squares up with Herceptin after HER2 bispecific aces mid-stage test in esophageal cancer
Roche’s Herceptin has long stood as standard of care across multiple advanced cancers, but a suite of next-gen players are looking to beat the aging giant at its own game. In HER2-expressing esophageal cancer, BeiGene partner Zymeworks thinks its bispecific antibody could have the juice to get it done.
Zymeworks’ bispecific antibody zanidatamab, combined with one of two chemotherapy regimens, posted an overall response rate of 75% in patients with advanced gastroesophageal adenocarcinoma (GEA) who had not previously received a HER2-targeted cancer therapy, the Vancouver-based biotech said Thursday.
The results from the Phase II study are set to be presented at this weekend’s #ESMO21 and look to set the battle lines between Zymeworks and partner BeiGene and Herceptin, the longtime standard of care in first-line advanced esophageal cancer.
Zymeworks intends to pursue a Phase III study based on these results looking in particular at the combination of zanidatamab and the chemo regimen known as CAPOX/FP. That combo posted a response rate of 93% in the Phase II study, which the partners see as a potential strong contender against Herceptin in this setting for the first time in years.
Meanwhile, the median duration of response was 16.4 months with a median progression-free survival of one year across all patients, Zymeworks said. At the cutoff, 61% of patients were still in the study.
Zymeworks thinks those efficacy and durability data stack up well against what Herceptin has shown in its own trials. In the Phase III TOGA trial, Herceptin plus chemo posted a 47.3% response rate in gastric or gastroesophageal junction cancers with a median PFS of around 7 months. Those results would appear to give zanidatamab the clear lead, but it’s important to note the data in Zymeworks’ open-label study were not powered for efficacy and the pool was fairly small — 36 patients total and 28 evaluable. A Phase III test, however, will put those results to the test.
That planned study, dubbed HERIZON-GEA-01, is set to open in the fourth quarter, and will test the zanidatamab-CAPOX combo with or without Novartis and BeiGene’s PD-1 inhibitor tislelizumab in a head-to-head matchup with the Herceptin-chemo standard of care in first-line advanced GEA.
Meanwhile, Zymeworks is also keeping an eye on evolving standard of care in this setting, with Merck and Roche’s collaboration on Keytruda plus Herceptin plus chemo in first-line esophageal cancer in the KEYNOTE-811 study currently ongoing. Zymeworks has its own Phase II study looking at zanidatamab plus chemo and PD-1 to keep up, but thinks its data with or without PD-1 can stack up well.
The rise of bispecific antibodies, an old-school drug concept that has only recently caught on with the FDA, has raised the prospect of challenging long-standing standards of care in advanced cancers, and zanidatamab’s case is no different. The drug, known as a “HER2xHER2” bispecific, works by simultaneously binding two non-overlapping HER2 epitopes — ECD2 and ECD4 — effectively offering a double down approach to targeting that well-known tumor target.
Zymeworks thinks zanidatamab could have a particularly strong effect in HER2 overexpressers, which make up just 20% of advanced GAE patients.
Back in November, the FDA offered a breakthrough designation for the drug in previously-treated HER2 gene-amplified biliary tract cancer based on the strength of its Phase I data.