Author: Dr. Shubham Pant, MD – MD Anderson
Overview: At the ASCO 2024 conference, Dr. Shubham Pant, MD – MD Anderson shared exciting updates from the Phase 2 trial of zanidatamab, a bispecific HER2 antibody, in patients with HER2-positive biliary tract cancer (BTC). This trial highlights the potential of zanidatamab to improve treatment outcomes for this challenging cancer type.
Mechanism of Action: Zanidatamab targets two domains on the HER2 protein (ECD2 and ECD4), which enhances receptor internalization and HER2 downregulation. This dual targeting mechanism leads to a more effective antitumor response compared to traditional HER2-targeted therapies.
Study Design:
- Global Trial: Included 80 patients with HER2 2+ or 3+ BTC.
- Administration: Zanidatamab was administered intravenously once every two weeks.
- Patient Population: Focused on those with third-line or later relapsed/refractory BTC.
Key Findings:
- Overall Response Rate (ORR): 41.3%, consistent with earlier results.
- Duration of Response (DoR): Increased to 14.9 months.
- Median Overall Survival (OS): 15.5 months.
- Comparison: Historically, FOLFOX chemotherapy has a response rate of only 5%, indicating a significant improvement with zanidatamab.
Safety Profile:
- Adverse Events: Mostly grade 1 and 2, with diarrhea being the most common, managed with anti-diarrheal agents and hydration.
- Severe Adverse Events: Few grade 3 and 4 events, with no grade 5 cytokine release syndrome or neurological events reported.
Future Directions: Encouraged by the Phase 2 results, zanidatamab is now being tested in first-line settings combined with gemcitabine, cisplatin, and immunotherapy for HER2-positive BTC. This expanded research aims to further validate its efficacy and safety in a broader patient population.
Conclusion: The Phase 2 trial results for zanidatamab are promising, showcasing its potential as a superior treatment option for HER2-positive biliary tract cancer. With a higher response rate and manageable safety profile, zanidatamab may significantly impact future clinical practices.
External Links:
ASCO Abstract: https://meetings.asco.org/abstracts-presentations/234212
Jazz Pharmaceuticals Press Release: https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-completes-zanidatamab-biologics-license
Dr. Shubham Pant, MD Bio: https://faculty.mdanderson.org/profiles/shubham_pant.html
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