Jazz Pharmaceuticals and Zymeworks Announce 84% Overall Survival at 18 Months from Phase 2 Trial Evaluating Zanidatamab in HER2-Expressing Metastatic Gastroesophageal Adenocarcinoma

Results presented today at ASCO GI include first overall survival (OS) data for zanidatamab, overall confirmed objective response rate (cORR) of 79%, disease control rate (DCR) of 92%, and median progression-free survival (mPFS) of 12.5 months

Ongoing Phase 3 randomized clinical trial, HERIZON-GEA-01, has the potential to support regulatory submissions for zanidatamab in combination with chemotherapy as a therapeutic option for patients with advanced HER2-expressing metastatic gastroesophageal adenocarcinoma (mGEA)

DUBLIN, Ireland and VANCOUVER, Canada I January 19, 2023 I Jazz Pharmaceuticals plc (Nasdaq: JAZZ) and Zymeworks Inc. (Nasdaq: ZYME) today announced tolerability and efficacy results, including the first overall survival (OS) data, from a Phase 2 trial examining zanidatamab, an investigational HER2-targeted bispecific antibody, in combination with chemotherapy, in first-line patients with HER2-expressing metastatic gastroesophageal adenocarcinoma (mGEA).

The preliminary results showed that, at the time of analysis, the median OS had not yet been reached with a median duration of study follow-up of 26.5 months. The 18-month overall survival rate was 84% [95% confidence interval (CI): 68%, 93%].

"Gastroesophageal adenocarcinoma represents one of the most frequent tumor types worldwide and, tragically, a leading cause of cancer-related deaths. Compared to what has historically been reported for OS with the current approved standard of care1, the OS findings from the combination of zanidatamab and chemotherapy in this trial are very compelling," said Dr. Elena Elimova, lead trial investigator and a medical oncologist at Princess Margaret Cancer Centre. "HER2 has been recognized as a predictive biomarker for these cancers, and it is promising to see a treatment targeting this expression exhibit strong and durable anti-tumor activity when administered with chemotherapy."

"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," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "These results showcase zanidatamab's potential as a foundational treatment for patients with HER2-positive mGEA, and we look forward to additional data in 2024 from the ongoing pivotal Phase 3 trial that may support U.S. and global regulatory filings."

Trial Results
The data include efficacy and tolerability findings from an ongoing, open-label Phase 2 study (NCT03929666) evaluating zanidatamab in combination with chemotherapy as first-line treatment for patients with advanced HER2-expressing mGEA, which is comprised of gastric, esophageal and gastroesophageal junction (GEJ) patients. Patients had not received prior HER2-targeted agents nor systemic treatment for mGEA. A total of 46 patients with mGEA were enrolled from 15 sites across the United States, Canada and South Korea, and patients were administered zanidatamab with physician's choice of chemotherapy treatment (standard first-line combination therapy). 

The data demonstrated zanidatamab combined with standard chemotherapy is a highly active treatment regimen for first-line therapy of HER2-positive mGEA. In 42 patients evaluable for OS receiving zanidatamab in combination with chemotherapy, the 18-month OS rate was 84% (95% CI: 68%, 93%), the 12-month OS rate was 88% (95% CI: 73%, 95%), and the median overall survival had not yet been reached (with 26.5 months median duration of study follow-up). Treatment with zanidatamab resulted in a confirmed objective response rate (cORR) of 79% (95% CI: 63-90%), a disease control rate (DCR) of 92% (95% CI: 79-98%), with three patients achieving complete response among 38 response-evaluable patients.

The median duration of response was 20.4 months (95% CI: 8.3-NE) with a median progression-free survival (mPFS) of 12.5 months (95% CI: 7.1-NE) with 17 patients having an ongoing response at the time of data cutoff. The regimen was manageable, tolerable and consistent with the observed safety profiles reported for other standard combination regimens for patients with HER2-positive GEA.

Data were presented in a poster session entitled Zanidatamab + Chemotherapy as First-Line Treatment for HER2-expressing Metastatic Gastroesophageal Adenocarcinoma (mGEA) during the American Society of Clinical Oncology's Gastrointestinal Cancers Symposium (ASCO GI) taking place in San Francisco. The presentation is available to conference registrants on the ASCO GI conference website (Abstract Number 347), and will be available to the general public on Zymeworks' website.

Zymeworks continues to enroll patients in the Phase 3 randomized clinical trial, HERIZON-GEA-01 (NCT05152147), evaluating zanidatamab in combination with chemotherapy plus or minus tislelizumab as a first-line treatment for HER2-expressing mGEA.

About Zanidatamab
Zanidatamab is an investigational 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 leading to encouraging antitumor activity in patients. Zymeworks, along with collaborators Jazz and BeiGene, Ltd. (BeiGene), are developing zanidatamab in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2.

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for zanidatamab in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC), and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for first-line GEA. Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.

About Gastroesophageal Adenocarcinoma
Gastroesophageal adenocarcinoma (GEA) is the fifth most common cancer worldwide, and approximately 20% of patients are HER2–positive.2,3,4 HER2–positive GEA has high morbidity and mortality, and patients are urgently in need of new treatment options.

About Jazz Pharmaceuticals plc
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharmaceutical company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with serious diseases—often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines and novel product candidates, from early- to late-stage development, in neuroscience and oncology. Within these therapeutic areas, we are identifying new options for patients by actively exploring small molecules and biologics, and through innovative delivery technologies and cannabinoid science. Jazz is headquartered in Dublin, Ireland and has employees around the globe, serving patients in nearly 75 countries. Please visit www.jazzpharmaceuticals.com for more information.

About Zymeworks Inc.
Zymeworks Inc. (Nasdaq: ZYME) is a global biotechnology company committed to the discovery, development, and commercialization of novel, multifunctional biotherapeutics. Zymeworks' mission is to make a meaningful difference for people impacted by difficult-to-treat cancers and other serious diseases. Zymeworks' complementary therapeutic platforms and fully integrated drug development engine provide the flexibility and compatibility to precisely engineer and develop highly differentiated antibody-based therapeutic candidates. Zymeworks engineered and developed zanidatamab, a HER2-targeted bispecific antibody using Zymeworks' proprietary Azymetric™ technology. Zymeworks has entered into separate agreements with BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting each of BeiGene and Jazz with exclusive rights to develop and commercialize zanidatamab in different territories. Zanidatamab is currently being evaluated in global Phase 1, Phase 2, and pivotal clinical trials as a treatment for patients with HER2-expressing cancers. Zymeworks' next clinical candidate, zanidatamab zovodotin (ZW49), is a HER2-targeted bispecific antibody-drug conjugate (ADC) developed using Zymeworks' proprietary Azymetric™ and ZymeLink™ Auristatin technologies. Zanidatamab zovodotin is currently being evaluated in a Phase 1 clinical trial for patients with a variety of HER2-expressing, HER2-amplified or HER2-mutant cancers. Zymeworks is also advancing a deep pipeline of product candidates based on its experience and capabilities in both ADC and multispecific antibodies (MSAT). In addition to Zymeworks' wholly-owned pipeline, its therapeutic platforms have been further leveraged through strategic partnerships with global biopharmaceutical companies. For information about Zymeworks, visit www.zymeworks.com and follow @ZymeworksInc on Twitter.

1 Bang, Y.J. et al., Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label randomised controlled trial. The Lancet. 2010;376(9742).
2 Abrahao-Machado I.F., et al. HER2 testing in gastric cancer: An update WorldJGastroenterol. 2016;22(19):4619-4625.
3 Van Custem E., et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18(3):476-484.
4 Stroes, C.I., et al. A systematic review of HER2 blockade for the curative treatment of gastroesophageal adenocarcinoma: Successes achieved and opportunities ahead. CancerTreatRev. 2021;99:102249.

SOURCE: Jazz Pharmaceuticals

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