On November 20, 2024, the FDA granted accelerated approval to zanidatamab-hrii (Ziihera), a bispecific HER2-directed antibody, for the treatment of previously treated, unresectable, or metastatic HER2-positive biliary tract cancer (BTC). This decision brings new hope for patients battling this aggressive and hard-to-treat disease, offering a targeted option for a population with limited therapeutic choices. The approval is based on promising results from the HERIZON-BTC-01 trial, and it marks a significant advancement in personalized oncology. Additionally, the FDA approved the VENTANA PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody as a companion diagnostic to identify eligible patients. This blog explores the details of the approval, efficacy, safety, and what it means for BTC care.
Biliary Tract Cancer and HER2-Positive Disease
Biliary tract cancer is a rare and aggressive cancer originating in the bile ducts, gallbladder, or ampulla of Vater. HER2 overexpression, found in approximately 5-15% of BTC cases, is associated with more aggressive disease and poorer outcomes. Prior to zanidatamab-hrii, treatment options for HER2-positive BTC were limited, with chemotherapy serving as the mainstay after disease progression.
This new approval addresses an unmet need, offering a targeted therapy for patients who have previously been treated with gemcitabine-containing regimens.
Efficacy of Zanidatamab-hrii: Results from the HERIZON-BTC-01 Trial
The approval is supported by data from HERIZON-BTC-01, a multicenter, single-arm, phase 2 trial that evaluated the efficacy and safety of zanidatamab-hrii in 62 patients with HER2-positive BTC. Patients had unresectable or metastatic disease and had previously received at least one gemcitabine-based chemotherapy regimen.
Key Findings:
- Objective Response Rate (ORR): 52% of patients experienced tumor shrinkage, a significant result for this population.
- Median Duration of Response (DOR): 14.9 months, with a confidence interval of 7.4 months to not estimable. This suggests durable benefits for responding patients.
- Disease Control: Many patients achieved sustained disease stabilization, highlighting zanidatamab-hrii’s potential to improve progression-free intervals.
These results underscore zanidatamab-hrii’s effectiveness in controlling disease progression in heavily pretreated patients.
Safety Profile and Administration
Zanidatamab-hrii was generally well-tolerated in the HERIZON-BTC-01 trial, with most side effects being manageable.
Most Common Adverse Reactions:
- Diarrhea
- Infusion-related reactions
- Abdominal pain
- Fatigue
Boxed Warning:
The prescribing information includes a boxed warning for embryo-fetal toxicity, highlighting the importance of pregnancy prevention for patients receiving this treatment.
Recommended Dosage:
The recommended dose is 20 mg/kg administered intravenously every 2 weeks. Treatment continues until disease progression or the emergence of unacceptable toxicity.
The Role of Companion Diagnostics
The FDA’s concurrent approval of the VENTANA PATHWAY anti-HER-2/neu (4B5) test ensures precision in identifying patients eligible for zanidatamab-hrii therapy. HER2 positivity, as determined by immunohistochemistry (IHC3+), is a critical requirement for treatment with this antibody. This precision-medicine approach aligns with the broader trend in oncology to match treatments to tumor biology.
What This Means for Patients
The accelerated approval of zanidatamab-hrii is a significant development for patients with HER2-positive BTC, a group previously underserved by available therapies. Key benefits include:
- Targeted Action: As a HER2-directed antibody, zanidatamab-hrii directly addresses the underlying tumor biology, improving outcomes for HER2-positive cancers.
- Durable Responses: With a median DOR of nearly 15 months, this therapy offers extended disease control for patients who respond.
- Personalized Approach: The integration of a companion diagnostic ensures that only patients likely to benefit from the therapy are treated.
Looking Ahead
While the approval of zanidatamab-hrii is a step forward, challenges remain in optimizing outcomes for BTC patients. Areas of future focus include:
- Combination Therapies: Investigating zanidatamab-hrii in combination with other immunotherapies or targeted agents.
- Broader Application: Evaluating its efficacy in earlier disease stages or in combination with standard chemotherapy.
- Long-Term Safety: Monitoring for potential long-term side effects as more patients are treated.
The FDA’s approval of zanidatamab-hrii for HER2-positive biliary tract cancer marks a meaningful advancement in personalized cancer care. For patients with limited options, this targeted therapy offers a chance for extended disease control and improved quality of life. As research progresses, innovations like this continue to pave the way for better outcomes in rare and challenging cancers.
For more updates on cancer treatments and breakthroughs, stay tuned to MedOncMD.com.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. He brings a wealth of expertise to the complex and challenging world of oncology.
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