Zanidatamab Shows Hopeful Results for Treating HER2-Positive Biliary Tract Cancer

Introduction to Biliary Tract Cancer

Biliary tract cancer is a rare yet aggressive form of cancer. It includes gallbladder cancer, extrahepatic cholangiocarcinoma, and intrahepatic cholangiocarcinoma. These cancers often go undetected until they are in advanced stages, making treatment challenging.

Understanding HER2-Positive Status

HER2, or Human Epidermal growth factor Receptor 2, is a protein that can promote the growth of cancer cells. In certain cancers, like biliary tract cancers, an overexpression or amplification of the HER2 gene is observed. This makes such cancers potential targets for HER2-inhibiting therapies.

Zanidatamab: A Promising Therapy

Zanidatamab is a bispecific antibody designed to target HER2. The recent phase 2B HERIZON-BTC-01 study presented at the ASCO Annual Meeting has shown promising results. Unlike traditional chemotherapy, zanidatamab specifically targets HER2-positive cancer cells, minimizing damage to normal cells.

Study Outcomes

The study included 87 patients with locally advanced or metastatic HER2-positive biliary tract cancer who had previously undergone treatment. Participants were divided into two cohorts based on their HER2 status as determined by immunohistochemistry (IHC) scores.

Results in Cohort 1

Cohort 1, comprising 80 patients with high HER2 expression (IHC2+/3+), showed an objective response rate (ORR) of 41.3%. This means about 41.3% of these patients had a significant reduction in tumor size. More importantly, the median overall survival (OS) for this group was approximately 15.5 months, which is far better than the usual 6-9 months seen with standard therapies.

Results in Cohort 2

Cohort 2 had lower HER2 expression levels and unfortunately showed no significant response to zanidatamab. This highlights the critical role of HER2 status in the efficacy of this targeted therapy.

Safety and Tolerability

Safety analyses indicated that most side effects were manageable. Common adverse effects included diarrhea, infusion-related reactions, and decrease in ejection fraction. Importantly, no treatment-related deaths occurred, suggesting the treatment is generally safe.

Implications for Future Treatment

These promising results support the need for next-generation sequencing in identifying patients who might benefit from HER2-targeted therapies. Subsequently, identifying HER2 amplification can make patients eligible for such targeted treatment approaches.

Regulatory Progress

In April, Jazz Pharmaceuticals submitted a biologics license application to the FDA for the accelerated approval of zanidatamab. Additionally, a phase 3 trial (HERIZON-BTC-02) is underway to assess zanidatamab in combination with standard therapies for first-line treatment.

Conclusion

The efficacy and safety profiles of zanidatamab indicate that it could become a viable non-chemotherapy option for patients with advanced HER2-positive biliary tract cancer. Researchers remain optimistic about the continuation of favorable results in upcoming trials.