FDA Approves Zanidatamab in HER2+ Biliary Tract Cancer

Biliary tract cancer: © Thipphaphone - stock.adobe.com

• The FDA granted an accelerated approval to zanidatamab-hrii (Ziihera) for the treatment of patients with previously treated, unresectable or metastatic HER2-positive (HER2+) biliary tract cancer.
• This is the first HER2-targeted treatment specifically approved in this disease state.
• The approval is supported by data from cohort 1 of the phase 2b HERIZON-BTC-01 trial (NCT04466891).

The HER2-targeted bispecific antibody zanidatamab is now FDA-approved for the treatment of adult patients with previously treated, unresectable or metastatic HER2+ (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.¹

The approval is supported by results from cohort 1 of the phase 2b HERIZON-BTC-01 trial, which showed that zanidatamab had an objective response rate (ORR) of 52% (95% CI, 39%-65%) and a median duration of response (DOR) of 14.9 months per independent central review (ICR) among 62 patients in this setting. Thirty patients had a partial response and 2 patients had a complete response.²

"As a clinical investigator and medical oncologist focused on advancing the care of patients with biliary tract and liver cancers, I have experienced firsthand the significant unmet need for effective therapies for patients with these diseases," said James Harding, MD associate attending, Gastrointestinal Oncology and Early Drug Development Services, at Memorial Sloan Kettering Cancer Center, in a press release.¹

"Zanidatamab has demonstrated antitumor activity and is now a new option for patients with HER2-positive biliary tract cancer. I look forward to continued and successful drug development for patients with biliary tract cancer," added Harding.¹

The efficacy population of cohort 1 from the open-label, multicenter global, phase 2b HERIZON-BTC-01 trial included 62 patients with HER2+ BTC with a median age of 64 years (range, 38-79).² To enroll in the trial, patients had to have received prior treatment with at least 1 gemcitabine-containing chemotherapy regimen for the treatment of advanced disease.

Results from the study were initially presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The Lancet Oncology. Here, the confirmed objective response rate (ORR) by independent central review was 41.3% (95% CI, 30.4%-52.8%).³

Updated findings were presented at the 2024 ASCO Annual Meeting and showed that, with a median follow-up of 21.9 months (range, 16-34), the confirmed ORR was unchanged from the primary analysis with 1 additional complete response.⁴ The median duration of response was 14.9 months (95% CI, 7.4-not reached). The median overall survival (OS) was 15.5 months (95% CI, 10.4-18.5), with a 12-month OS rate of 56.2% (95% CI, 44.3%-66.5%).

More specific OS data from cohort 1 showed that in patients with IHC 2+, the median OS was 5.2 months (95% CI, 3.1-10.2), with a 6-month OS rate of 41.7% (95% CI, 17.5%-64.4%) and a 12-month OS rate of 20.8% (95% CI, 5.1%-43.7%). In those with IHC 3+, the median OS was 18.1 months (95% CI, 12.2-23.2), and the 6- and 12-month OS rates were 90.1% (95% CI, 79.2%-95.4%) and 65.0% (95% CI, 51.6%-75.6%), respectively.⁴

Regarding safety, the prescribing label for zanidatamab lists that in the 80-patient safety population, adverse events (AEs) occurring in at least 20% of patients were diarrhea, infusion-related reaction, abdominal pain, and fatigue.² Serious AEs (SAEs) occurred in 53% of patients receiving zanidatamab. The most common SAEs were biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%), and fatigue (2.5%). In this safety population, 2.5% of patients permanently discontinued zanidatamab due to an AE, and 1 patient treated with zanidatamab had a fatal AE.

The ongoing, international, phase 3 HERIZON-BTC-02 trial (NCT06282575) is evaluating frontline zanidatamab in combination with standard cisplatin/gemcitabine with or without a PD-1/PD-L1 inhibitor in patients with advanced HER2+ biliary tract cancer.¹

REFERENCES:

1. Jazz Pharmaceuticals Announces U.S. FDA Approval of Ziihera® (zanidatamab-hrii) for the Treatment of Adults with Previously Treated, Unresectable or Metastatic HER2-positive (IHC 3+) Biliary Tract Cancer (BTC). Published online November 20, 2024. Accessed November 21, 2024. https://tinyurl.com/3vt9ka3b

2. Prescribing Label: ZIIHERA® (zanidatamab-hrii) for injection, for intravenous use.
Initial U.S. Approval: 2024. Accessed November 21, 2024. https://pp.jazzpharma.com/pi/ziihera.en.USPI.pdf

3. Jazz Pharmaceuticals and Zymeworks Present Positive Pivotal Phase 2b Trial Data at ASCO 2023 Evaluating Zanidatamab in HER2-Amplified Biliary Tract Cancers. Published online June 2, 2023. Accessed November 21, 2024. https://tinyurl.com/4zud3edx

4. Pant S, Fan J, Oh D, et al. Zanidatamab in previously-treated HER2-positive (HER2+) biliary tract cancer (BTC): Overall survival (OS) and longer follow-up from the phase 2b HERIZON-BTC-01 study. J Clin Oncol. 2024;42(suppl 16):abstr 4091). doi:10.1200/JCO.2024.42.16_suppl.409