Jazz Pharmaceuticals has posted fresh phase 2 data on zanidatamab that show the HER2-targeted bispecific antibody kept 59% of people with metastatic gastroesophageal cancer (mGEA) alive for at least 30 months when given in combination with chemotherapy. These results were presented at the European Society for Medical Oncology conference in Barcelona, Spain. This positive data follows the release of 18-month data from the same phase 2 trial earlier this year, which showed an overall survival (OS) rate of 84%.
Jazz’s Global Head of R&D, Robert Iannone, M.D., highlighted the significance of the 30-month data, stating that they “reaffirm zanidatamab’s potential as a foundational treatment for patients with HER2-positive mGEA and showcase the promise of this HER2-targeted bispecific antibody to treat HER2-expressing cancers.” The data also showed a confirmed objective response rate (cORR) of 84%, a 5% increase from the 79% cORR reported in the 18-month data. Additionally, the median duration of response (DoR) was 18.7 months, and the median progression-free survival (PFS) was 15.2 months. One additional patient achieved a complete response since the 18-month readout, bringing the total number of patients who achieved this to four out of 37 response-evaluable patients.
While Jazz has not directly compared zanidatamab to other oncology treatments in head-to-head trials, Iannone believes the data on ORR, DoR, PFS, and OS are comparable to the front-line standard of care with Herceptin plus chemotherapy. The potential to treat GEA by targeting HER2 was confirmed in 2010 when researchers showed that adding Roche’s Herceptin to chemotherapy extended OS from 11.1 months to 13.8 months.
The safety profile of zanidatamab in combination with chemotherapy remains manageable. There were no treatment-related deaths in the 30-month data, and discontinuations due to treatment-related adverse events affected only two out of 46 evaluable patients. A total of 63% of patients experienced an adverse event of grade 3 or above, with diarrhea being the most common, affecting 35% of patients. “With additional follow-up, the safety and tolerability profile of zanidatamab plus chemotherapy in all patients assessed remained manageable with no new safety signals identified compared to the previous analysis,” Iannone said.
Jazz is continuing to enroll patients in a phase 3 trial of zanidatamab in combination with chemotherapy and BeiGene’s Tevimbra as a first-line treatment for HER2-positive mGEA. A topline readout is expected in the second quarter of 2025. In the meantime, Jazz is awaiting the FDA’s decision on the approval of zanidatamab to treat previously treated, unresectable, locally advanced or metastatic HER2-positive biliary tract cancer. If the regulator gives the nod in November, the Zymeworks-partnered bispecific antibody would be the first HER2-targeted treatment specifically for the indication.
Zanidatamab's Promise in Colorectal Cancer
Beyond its potential in gastroesophageal cancer, zanidatamab has also shown promise in colorectal cancer. Data from a phase 2 study evaluating zanidatamab in combination with chemotherapy and bevacizumab as first-line treatment in HER2-positive metastatic colorectal cancer, presented at the 2024 ESMO Congress, highlighted encouraging antitumor activity.
The study, led by Sun Young Rha, MD, director of Songdang Institute for Cancer Research, Yonsei University College of Medicine, Yonsei University Health System in Seoul, Korea, enrolled patients with unresectable, locally advanced, recurrent, or metastatic colorectal cancer. Patients had to have HER2-expressing (immunohistochemistry IHC 3+) or HER2-amplified disease per central assessment. The primary end points of the study included dose-limiting toxicities (DLTs), adverse events (AEs), laboratory abnormalities, and dose reductions; secondary end points consisted of overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS).
Key Findings from the Phase 2 Trial
The results were promising. At a median follow-up of 15.4 months, the confirmed overall response rate (cORR) was 83.3% in patients treated with zanidatamab plus mFOLFOX6-2 (n = 6). All responders achieved a partial response (PR), and the lone non-responder had stable disease. The cORR was 100% in the zanidatamab plus mFOLFOX6-2 and bevacizumab arm (n = 5). Across both treatment arms, the cORR was 90.9%, and the disease control rate was 100%. The median DOR for the overall population was not reached (NR; range, 2.9+ to 16.7+).
Safety Profile of Zanidatamab in Colorectal Cancer
The safety profile of zanidatamab in combination with chemotherapy in colorectal cancer was generally manageable. Two DLTs of diarrhea were documented—one in each treatment group—and resolved with concomitant medication. Serious treatment-related adverse effects (TRAEs) were noted in 15.4% of patients (n = 2), including one patient who experienced dehydration and another patient who had colitis and an acute kidney injury. However, no patients discontinued zanidatamab due to TRAEs, and no treatment-related deaths were reported.
“Zanidatamab in combination with chemotherapy showed encouraging antitumor activity with a generally manageable safety profile as a first-line treatment for patients with HER2-positive mCRC,” Rha stated. These findings suggest that zanidatamab may be a promising new treatment option for patients with HER2-positive metastatic colorectal cancer, offering a potential for improved outcomes and manageable side effects.
Looking Ahead: The Future of Zanidatamab
As Jazz Pharmaceuticals continues to gather data on zanidatamab, it is clear that this HER2-targeted bispecific antibody has the potential to significantly impact the treatment of HER2-positive cancers. With encouraging results in both gastroesophageal and colorectal cancers, zanidatamab represents a promising new therapeutic option for patients with these challenging diseases. Its unique mechanism of action and manageable safety profile make it a valuable addition to the oncologist’s arsenal, paving the way for a future where HER2-positive cancers are more effectively managed and treated.
