Jazz Pharmaceuticals Shares HERIZON-BTC-01 Trial Data on Zanidatamab for HER2+ Biliary Tract Cancer at ASCO 2024

Jazz Pharmaceuticals has announced significant long-term results from their Phase 2b HERIZON-BTC-01 clinical trial investigating zanidatamab, a HER2-targeted bispecific antibody, in patients with advanced HER2-positive biliary tract cancer (BTC). The findings will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2024.

The study revealed median overall survival (OS) of 15.5 months for patients with centrally confirmed IHC 2+ or 3+ tumors and 18.1 months for those with IHC 3+ tumors. The median duration of response (DoR) extended by two months from initial analysis to 14.9 months, demonstrating the sustained efficacy of zanidatamab.

Clinical Trial Overview

The HERIZON-BTC-01 trial focused on previously treated, unresectable, locally advanced, or metastatic HER2-positive BTC patients. Participants received zanidatamab (20 mg/kg IV every two weeks) after prior gemcitabine-based therapy. The trial excluded patients with previous HER2-targeted treatments, and tumors were assessed every eight weeks per RECIST v1.1 guidelines.

Initial findings showcased a confirmed objective response rate (cORR) of 41.3%, with one additional patient achieving complete response since the ASCO 2023 presentation. The updated data includes a median OS of 15.5 months for all HER2-positive BTC patients, with a higher survival rate of 18.1 months for IHC 3+ tumors and 5.2 months for IHC 2+ tumors.

Expert Insights

Dr. Shubham Pant from MD Anderson Cancer Center highlighted the importance of these findings. He noted that patients with advanced BTC often face poor prognoses, with standard chemotherapy offering only 6-9 months of survival. Zanidatamab’s deep and durable responses suggest a significant advancement in treating HER2-expressing BTC without chemotherapy.

Future Directions

Rob Iannone of Jazz Pharmaceuticals emphasized the potential of zanidatamab in fulfilling unmet needs for advanced HER2-positive BTC treatments. The data from HERIZON-BTC-01 has been included in a Biologics License Application (BLA) for FDA Priority Review and a Marketing Authorization Application to the European Medicines Agency. Jazz is also conducting the HERIZON-BTC-302 trial, a global Phase 3 study evaluating zanidatamab with standard therapy for first-line HER2-positive BTC patients.

Updated Trial Outcomes

Extended follow-up data as of July 28, 2023, showed:
- cORR sustained at 41.3% with one additional complete response.
- Median DoR increased to 14.9 months, with 7.5 months for the one responder with IHC 2+ tumors.
- Median OS of 15.5 months for all HER2-positive BTC patients, 18.1 months for IHC 3+ tumors, and 5.2 months for IHC 2+ tumors.
- Median progression-free survival (PFS) maintained at 5.5 months.

Safety Profile

Zanidatamab maintained a favorable safety profile with manageable tolerability. Only 2.3% of patients discontinued treatment due to adverse events, and no new safety signals were identified.

About Zanidatamab

Zanidatamab is an investigational bispecific antibody targeting HER2, developed by Jazz and BeiGene under a license from Zymeworks. It binds two non-overlapping HER2 epitopes, enhancing its antitumor activity through multiple mechanisms including HER2 signal blockade, protein removal from the cell surface, and immune-mediated cytotoxicity.

The FDA has granted Priority Review for zanidatamab’s BLA with a decision expected by November 29, 2024. It has also received Breakthrough Therapy and Orphan Drug designations for BTC and other cancers.

Conclusion

The promising results of zanidatamab in treating HER2-positive BTC mark a potential breakthrough for patients with limited options. With ongoing trials and regulatory reviews, zanidatamab could soon emerge as a critical treatment for HER2-expressing cancers.

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