Tislelizumab

Zymeworks and Jazz Pharmaceuticals said that the addition of their HER2 bispecific Ziihera helped stave off disease progression in certain patients with gastroesophageal adenocarcinoma — a type of cancer that occurs in the stomach, esophagus and the area where the two meet. And in a subset that got Ziihera plus BeOne Medicines’ Tevimbra, the patients lived for longer than those who got standard treatments. The overall survival benefit for those patients was statistically significant. Both progression-free survival and overall survival were primary endpoints in the study. It’s the first Phase 3 trial readout for Ziihera, and it appears to be a resounding success. Jazz plans to file for approval based on the study in the first half of 2026. The 914-patient study, known as HERIZON-GEA-01, looked at two Ziihera combinations as first-line options in patients with advanced HER2-positive gastroesophageal cancer. One of the combinations tested was Ziihera plus chemotherapy, while the other included those two treatments plus Tevimbra. A third comparator arm included the current standard treatment of trastuzumab (sold under the brand name Herceptin, among others) plus chemotherapy. The companies said the Ziihera and chemotherapy arm also showed a “strong trend toward statistical significance” for overall survival, and the study is continuing with another survival readout for the Ziihera-chemotherapy arm expected in mid-2026. Jazz first won FDA approval last year for the HER2 bispecific in biliary tract cancer. The drug was first developed at Zymeworks and is being commercialized by Jazz in the US, Europe and Japan, among other markets, and by BeOne, formerly Beigene, in Asia/Pacific countries (except Japan). Zymeworks’ stock $ZYME jumped 30% Monday, and Jazz’s $JAZZ rose 20%. BeOne’s shares increased by 3%.

Jazz Pharmaceuticals plans to submit the results for presentation at an upcoming medical meeting and to the FDA. Three years after striking up a Zymeworks licensing pact with an eye on challenging the status quo in HER2-positive cancers, Jazz Pharmaceuticals is seeing its vision with Ziihera come into clearer focus.In a press release Monday, Jazz described a positive phase 3 readout as boosting its confidence that it has a HER2-targeted "agent-of-choice" for first-line patients with HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma (GEA), including cancers of the stomach, gastroesophageal junction and esophagus.For a combination of Ziihera plus chemotherapy and BeOne Medicines' Tevimbra, Jazz sees a "new standard of care" coming into form.The HERIZON-GEA-01 study, conducted with BeOne, is assessing Jazz's HER2-targeted bispecific in doublet and triplet regimens. The doublet pairs the Jazz drug with chemo, while the triplet adds BeOne's PD-1 inhibitor Tevimbra.The comparator arm in the study is the current standard of care, the combination of Roche's Herceptin and chemotherapy, Jazz said.In the topline readout revealed Monday, Jazz said patients treated with Ziihera plus chemotherapy experienced a "clinically meaningful and statistically significant" improvement in progression-free survival (PFS) versus those in the comparator arm. On the crucial overall survival (OS) measure, the company described a "clinically meaningful effect with a strong trend toward statistical significance" at the first interim analysis. Another OS analysis is expected in the ongoing trial next year, the company added.For the triplet regimen, the trial showed "clinically meaningful and statistically significant improvements" in both OS and PFS, Jazz said. The benefits were seen across both the PD-L1-positive and PD-L1-negative subgroups, according to Jazz.Jazz will now get to work submitting the data for presentation at a medical meeting next year and for publication in a peer-reviewed scientific journal. In addition, the company plans to submit an FDA filing in the first half of next year in pursuit of approvals for both the doublet and triplet regimens, Jazz Chief Medical Officer Rob Iannone, M.D., said in a statement."We believe these results will be practice changing, and highlight the potential impact of Ziihera for patients who are facing a devastating diagnosis and limited options in locally advanced or metastatic GEA," Iannone added.The company will also work to get the regimens into the National Comprehensive Cancer Network treatment guidelines.Ziihera won its original FDA approval a year ago as a treatment for adults with previously treated HER2-positive biliary tract cancer. At the time, then-CEO Bruce Cozadd told Fierce Pharma that Jazz believed the drug could generate more than $2 billion in peak sales, singling out opportunities in HER2-positive stomach cancer and breast cancer. Jazz got its hands on the drug as part of a 2022 licensing agreement with Zymeworks, paying $50 million upfront and committing up to $1.76 billion in milestones at the time. In making that deal, the company touted the asset's bispecific construct and its "potential to transform the current standard of care in multiple HER2 expressing cancers," Iannone said in a statement.A couple of firsts are in play with the HERIZON-GEA-01 trial. Besides being the first phase 3 study for Jazz's Ziihera, it's also the first phase 3 to show a benefit for a novel HER-2 targeted therapy against a Herceptin-based combination in patients with  first-line HER2-positive GEA.The safety profile of the investigational regimens was expected, with "no new safety signals observed," Jazz said. In a note to clients Monday, Mizuho analyst Salim Syed wrote that both the doublet and triplet arms "seem to look very strong," boosting his confidence that Zymeworks will see remaining regulatory milestones from its Jazz deal.In early trading Monday, Jazz's shares were up about 20%, while Zymeworks' share price spiked by some 35%.